Regeneration (biology)

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Sunflower sea star regenerates its arms. Sea star regenerating legs.jpg
Sunflower sea star regenerates its arms.
Dwarf yellow-headed gecko with regenerating tail Dwarf Yellow-headed gecko edit.jpg
Dwarf yellow-headed gecko with regenerating tail

Regeneration in biology is the process of renewal, restoration, and tissue growth that makes genomes, cells, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. [1] Every species is capable of regeneration, from bacteria to humans. [2] [3] [4] Regeneration can either be complete [5] where the new tissue is the same as the lost tissue, [5] or incomplete [6] after which the necrotic tissue becomes fibrotic. [6]

Contents

At its most elementary level, regeneration is mediated by the molecular processes of gene regulation and involves the cellular processes of cell proliferation, morphogenesis and cell differentiation. [7] [8] Regeneration in biology, however, mainly refers to the morphogenic processes that characterize the phenotypic plasticity of traits allowing multi-cellular organisms to repair and maintain the integrity of their physiological and morphological states. Above the genetic level, regeneration is fundamentally regulated by asexual cellular processes. [9] Regeneration is different from reproduction. For example, hydra perform regeneration but reproduce by the method of budding.

The regenerative process occurs in two multi-step phases: the preparation phase and the redevelopment phase. [10] [11] Regeneration begins with an amputation which triggers the first phase. Right after the amputation, migrating epidermal cells form a wound epithelium which thickens, through cell division, throughout the first phase to form a cap around the site of the wound. [10] The cells underneath this cap then begin to rapidly divide and form a cone shaped end to the amputation known as a blastema. Included in the blastema are skin, muscle, and cartilage cells that de-differentiate and become similar to stem cells in that they can become multiple types of cells. Cells differentiate to the same purpose they originally filled meaning skin cells again become skin cells and muscle cells become muscles. These de-differentiated cells divide until enough cells are available at which point they differentiate again and the shape of the blastema begins to flatten out. It is at this point that the second phase begins, the redevelopment of the limb. In this stage, genes signal to the cells to differentiate themselves and the various parts of the limb are developed. The end result is a limb that looks and operates identically to the one that was lost, usually without any visual indication that the limb is newly generated.

The hydra and the planarian flatworm have long served as model organisms for their highly adaptive regenerative capabilities. [12] Once wounded, their cells become activated and restore the organs back to their pre-existing state. [13] The Caudata ("urodeles"; salamanders and newts), an order of tailed amphibians, is possibly the most adept vertebrate group at regeneration, given their capability of regenerating limbs, tails, jaws, eyes and a variety of internal structures. [2] The regeneration of organs is a common and widespread adaptive capability among metazoan creatures. [12] In a related context, some animals are able to reproduce asexually through fragmentation, budding, or fission. [9] A planarian parent, for example, will constrict, split in the middle, and each half generates a new end to form two clones of the original. [14]

Echinoderms (such as the sea star), crayfish, many reptiles, and amphibians exhibit remarkable examples of tissue regeneration. The case of autotomy, for example, serves as a defensive function as the animal detaches a limb or tail to avoid capture. After the limb or tail has been autotomized, cells move into action and the tissues will regenerate. [15] [16] [17] In some cases a shed limb can itself regenerate a new individual. [18] Limited regeneration of limbs occurs in most fishes and salamanders, and tail regeneration takes place in larval frogs and toads (but not adults). The whole limb of a salamander or a triton will grow repeatedly after amputation. In reptiles, chelonians, crocodilians and snakes are unable to regenerate lost parts, but many (not all) kinds of lizards, geckos and iguanas possess regeneration capacity in a high degree. Usually, it involves dropping a section of their tail and regenerating it as part of a defense mechanism. While escaping a predator, if the predator catches the tail, it will disconnect. [19]

Ecosystems

Ecosystems can be regenerative. Following a disturbance, such as a fire or pest outbreak in a forest, pioneering species will occupy, compete for space, and establish themselves in the newly opened habitat. The new growth of seedlings and community assembly process is known as regeneration in ecology. [20] [21]

Cellular molecular fundamentals

Pattern formation in the morphogenesis of an animal is regulated by genetic induction factors that put cells to work after damage has occurred. Neural cells, for example, express growth-associated proteins, such as GAP-43, tubulin, actin, an array of novel neuropeptides, and cytokines that induce a cellular physiological response to regenerate from the damage. [22] Many of the genes that are involved in the original development of tissues are reinitialized during the regenerative process. Cells in the primordia of zebrafish fins, for example, express four genes from the homeobox msx family during development and regeneration. [23]

Tissues

"Strategies include the rearrangement of pre-existing tissue, the use of adult somatic stem cells and the dedifferentiation and/or transdifferentiation of cells, and more than one mode can operate in different tissues of the same animal. [1] All these strategies result in the re-establishment of appropriate tissue polarity, structure and form." [24] : 873  During the developmental process, genes are activated that serve to modify the properties of cell as they differentiate into different tissues. Development and regeneration involves the coordination and organization of populations cells into a blastema, which is "a mound of stem cells from which regeneration begins". [25] Dedifferentiation of cells means that they lose their tissue-specific characteristics as tissues remodel during the regeneration process. This should not be confused with the transdifferentiation of cells which is when they lose their tissue-specific characteristics during the regeneration process, and then re-differentiate to a different kind of cell. [24]

In animals

Arthropods

Limb regeneration

Many arthropods can regenerate limbs and other appendages following either injury or autotomy. [26] Regeneration capacity is constrained by the developmental stage and ability to molt.

Crustaceans, which continually molt, can regenerate throughout their lifetimes. [27] While molting cycles are generally hormonally regulated, limb amputation induces premature molting. [26] [28]

Hemimetabolous insects such as crickets can regenerate limbs as nymphs, before their final molt. [29]

Holometabolous insects can regenerate appendages as larvae prior to the final molt and metamorphosis. Beetle larvae, for example, can regenerate amputated limbs. Fruit fly larvae do not have limbs but can regenerate their appendage primordia, imaginal discs. [30] In both systems, the regrowth of the new tissue delays pupation. [30] [31]

Mechanisms underlying appendage limb regeneration in insects and crustaceans are highly conserved. [32] During limb regeneration species in both taxa form a blastema that proliferates and grows to repattern the missing tissue. [33]

Venom regeneration

Arachnids, including scorpions, are known to regenerate their venom, although the content of the regenerated venom is different from the original venom during its regeneration, as the venom volume is replaced before the active proteins are all replenished. [34]

Fruit fly model

The fruit fly Drosophila melanogaster is a useful model organism to understand the molecular mechanisms that control regeneration, especially gut and germline regeneration. [30] In these tissues, resident stem cells continually renew lost cells. [30] The Hippo signaling pathway was discovered in flies and was found to be required for midgut regeneration. Later, this conserved signaling pathway was also found to be essential for regeneration of many mammalian tissues, including heart, liver, skin, and lung, and intestine. [35]

Annelids

Many annelids (segmented worms) are capable of regeneration. [36] For example, Chaetopterus variopedatus and Branchiomma nigromaculata can regenerate both anterior and posterior body parts after latitudinal bisection. [37] The relationship between somatic and germline stem cell regeneration has been studied at the molecular level in the annelid Capitella teleta . [38] Leeches, however, appear incapable of segmental regeneration. [39] Furthermore, their close relatives, the branchiobdellids, are also incapable of segmental regeneration. [39] [36] However, certain individuals, like the lumbriculids, can regenerate from only a few segments. [39] Segmental regeneration in these animals is epimorphic and occurs through blastema formation. [39] Segmental regeneration has been gained and lost during annelid evolution, as seen in oligochaetes, where head regeneration has been lost three separate times. [39]

Along with epimorphosis, some polychaetes like Sabella pavonina experience morphallactic regeneration. [39] [40] Morphallaxis involves the de-differentiation, transformation, and re-differentation of cells to regenerate tissues. How prominent morphallactic regeneration is in oligochaetes is currently not well understood. Although relatively under-reported, it is possible that morphallaxis is a common mode of inter-segment regeneration in annelids. Following regeneration in L. variegatus, past posterior segments sometimes become anterior in the new body orientation, consistent with morphallaxis.

Following amputation, most annelids are capable of sealing their body via rapid muscular contraction. Constriction of body muscle can lead to infection prevention. In certain species, such as Limnodrilus , autolysis can be seen within hours after amputation in the ectoderm and mesoderm. Amputation is also thought to cause a large migration of cells to the injury site, and these form a wound plug.

Echinoderms

Tissue regeneration is widespread among echinoderms and has been well documented in starfish (Asteroidea), sea cucumbers (Holothuroidea), and sea urchins (Echinoidea). Appendage regeneration in echinoderms has been studied since at least the 19th century. [41] In addition to appendages, some species can regenerate internal organs and parts of their central nervous system. [42] In response to injury starfish can autotomize damaged appendages. Autotomy is the self-amputation of a body part, usually an appendage.  Depending on severity, starfish will then go through a four-week process where the appendage will be regenerated. [43] Some species must retain mouth cells to regenerate an appendage, due to the need for energy. [44] The first organs to regenerate, in all species documented to date, are associated with the digestive tract. Thus, most knowledge about visceral regeneration in holothurians concerns this system. [45]

Planaria (Platyhelminthes)

Regeneration research using Planarians began in the late 1800s and was popularized by T.H. Morgan at the beginning of the 20th century. [44] Alejandro Sanchez-Alvarado and Philip Newmark transformed planarians into a model genetic organism in the beginning of the 20th century to study the molecular mechanisms underlying regeneration in these animals. [46] Planarians exhibit an extraordinary ability to regenerate lost body parts. For example, a planarian split lengthwise or crosswise will regenerate into two separate individuals. In one experiment, T.H. Morgan found that a piece corresponding to 1/279th of a planarian [44] or a fragment with as few as 10,000 cells can successfully regenerate into a new worm within one to two weeks. [47] After amputation, stump cells form a blastema formed from neoblasts, pluripotent cells found throughout the planarian body. [48] New tissue grows from neoblasts with neoblasts comprising between 20 and 30% of all planarian cells. [47] Recent work has confirmed that neoblasts are totipotent since one single neoblast can regenerate an entire irradiated animal that has been rendered incapable of regeneration. [49] In order to prevent starvation a planarian will use their own cells for energy, this phenomenon is known as de-growth. [13]

Amphibians

Limb regeneration in the axolotl and newt has been extensively studied and researched. The nineteenth century studies of this subject are reviewed in Holland (2021). [50] Urodele amphibians, such as salamanders and newts, display the highest regenerative ability among tetrapods. [51] [50] As such, they can fully regenerate their limbs, tail, jaws, and retina via epimorphic regeneration leading to functional replacement with new tissue. [52] Salamander limb regeneration occurs in two main steps. First, the local cells dedifferentiate at the wound site into progenitor to form a blastema. [53] Second, the blastemal cells will undergo cell proliferation, patterning, cell differentiation and tissue growth using similar genetic mechanisms that deployed during embryonic development. [54] Ultimately, blastemal cells will generate all the cells for the new structure. [51]

Axolotls can regenerate a variety of structures, including their limbs. AxolotlBE.jpg
Axolotls can regenerate a variety of structures, including their limbs.

After amputation, the epidermis migrates to cover the stump in 1–2 hours, forming a structure called the wound epithelium (WE). [55] Epidermal cells continue to migrate over the WE, resulting in a thickened, specialized signaling center called the apical epithelial cap (AEC). [56] Over the next several days there are changes in the underlying stump tissues that result in the formation of a blastema (a mass of dedifferentiated proliferating cells). As the blastema forms, pattern formation genes – such as HoxA and HoxD – are activated as they were when the limb was formed in the embryo. [57] [58] The positional identity of the distal tip of the limb (i.e. the autopod, which is the hand or foot) is formed first in the blastema. Intermediate positional identities between the stump and the distal tip are then filled in through a process called intercalation. [57] Motor neurons, muscle, and blood vessels grow with the regenerated limb, and reestablish the connections that were present prior to amputation. The time that this entire process takes varies according to the age of the animal, ranging from about a month to around three months in the adult and then the limb becomes fully functional. Researchers at Australian Regenerative Medicine Institute at Monash University have published that when macrophages, which eat up material debris, [59] were removed, salamanders lost their ability to regenerate and formed scarred tissue instead. [60] The axolotl salamander Ambystoma mexicanum , an organism with exceptional limb regenerative capabilities, likely undergoes epigenetic alterations in its blastema cells that enhance expression of genes involved in limb regeneration. The Axolotl has very little blood and has an excess of epidermal cells. This allows the affected area to then flourish with epidermal cells and continued gene expression allows the area to regenerate to its natural being. [61]

In spite of the historically few researchers studying limb regeneration, remarkable progress has been made recently in establishing the neotenous amphibian the axolotl (Ambystoma mexicanum) as a model genetic organism. This progress has been facilitated by advances in genomics, bioinformatics, and somatic cell transgenesis in other fields, that have created the opportunity to investigate the mechanisms of important biological properties, such as limb regeneration, in the axolotl. [54] The Ambystoma Genetic Stock Center (AGSC) is a self-sustaining, breeding colony of the axolotl supported by the National Science Foundation as a Living Stock Collection. Located at the University of Kentucky, the AGSC is dedicated to supplying genetically well-characterized axolotl embryos, larvae, and adults to laboratories throughout the United States and abroad. An NIH-funded NCRR grant has led to the establishment of the Ambystoma EST database, the Salamander Genome Project (SGP) that has led to the creation of the first amphibian gene map and several annotated molecular data bases, and the creation of the research community web portal. [62] In 2022, a first spatiotemporal map revealed key insights about axolotl brain regeneration, also providing the interactive Axolotl Regenerative Telencephalon Interpretation via Spatiotemporal Transcriptomic Atlas. [63] [64]

Frog model

Anurans (frogs) can only regenerate their limbs during embryonic development. [65] Reactive oxygen species (ROS) appear to be required for a regeneration response in the anuran larvae. [66] ROS production is essential to activate the Wnt signaling pathway, which has been associated with regeneration in other systems. [66]

Once the limb skeleton has developed in frogs, regeneration does not occur (Xenopus can grow a cartilaginous spike after amputation). [65] The adult Xenopus laevis is used as a model organism for regenerative medicine. In 2022, a cocktail of drugs and hormones (1,4-DPCA, BDNF, growth hormone, resolvin D5, and retinoic acid), in a single dose lasting 24 hours, was shown to trigger long-term leg regeneration in adult X. laevis. Instead of a single spike, a paddle-shaped growth is obtained at the end of the limb by 18 months. [67]

Hydra

Hydra is a genus of freshwater polyp in the phylum Cnidaria with highly proliferative stem cells that gives them the ability to regenerate their entire body. [68] Any fragment larger than a few hundred epithelial cells that is isolated from the body has the ability to regenerate into a smaller version of itself. [68] The high proportion of stem cells in the hydra supports its efficient regenerative ability. [69]

Regeneration among hydra occurs as foot regeneration arising from the basal part of the body, and head regeneration, arising from the apical region. [68] Regeneration tissues that are cut from the gastric region contain polarity, which allows them to distinguish between regenerating a head in the apical end and a foot in the basal end so that both regions are present in the newly regenerated organism. [68] Head regeneration requires complex reconstruction of the area, while foot regeneration is much simpler, similar to tissue repair. [70] In both foot and head regeneration, however, there are two distinct molecular cascades that occur once the tissue is wounded: early injury response and a subsequent, signal-driven pathway of the regenerating tissue that leads to cellular differentiation. [69] This early-injury response includes epithelial cell stretching for wound closure, the migration of interstitial progenitors towards the wound, cell death, phagocytosis of cell debris, and reconstruction of the extracellular matrix. [69]

Regeneration in hydra has been defined as morphallaxis, the process where regeneration results from remodeling of existing material without cellular proliferation. [71] [72] If a hydra is cut into two pieces, the remaining severed sections form two fully functional and independent hydra, approximately the same size as the two smaller severed sections. [68] This occurs through the exchange and rearrangement of soft tissues without the formation of new material. [69]

During Hydra head regeneration there are coordinated gene expression and chromatin regulation changes. [73] An enhancer is a short DNA sequence (50–1500 base pairs) that can be bound by transcription factors to increase the transcription of a particular gene. In the enhancer regions that are activated during head regeneration, a set of transcription factor motifs commonly occur that appear to facilitate coordinated gene expression. [73]

Aves (birds)

Owing to a limited literature on the subject, birds are believed to have very limited regenerative abilities as adults. Some studies [74] on roosters have suggested that birds can adequately regenerate some parts of the limbs and depending on the conditions in which regeneration takes place, such as age of the animal, the inter-relationship of the injured tissue with other muscles, and the type of operation, can involve complete regeneration of some musculoskeletal structure. Werber and Goldschmidt (1909) found that the goose and duck were capable of regenerating their beaks after partial amputation [74] and Sidorova (1962) observed liver regeneration via hypertrophy in roosters. [75] Birds are also capable of regenerating the hair cells in their cochlea following noise damage or ototoxic drug damage. [76] Despite this evidence, contemporary studies suggest reparative regeneration in avian species is limited to periods during embryonic development. An array of molecular biology techniques have been successful in manipulating cellular pathways known to contribute to spontaneous regeneration in chick embryos. [77] For instance, removing a portion of the elbow joint in a chick embryo via window excision or slice excision and comparing joint tissue specific markers and cartilage markers showed that window excision allowed 10 out of 20 limbs to regenerate and expressed joint genes similarly to a developing embryo. In contrast, slice excision did not allow the joint to regenerate due to the fusion of the skeletal elements seen by an expression of cartilage markers. [78]

Similar to the physiological regeneration of hair in mammals, birds can regenerate their feathers in order to repair damaged feathers or to attract mates with their plumage. Typically, seasonal changes that are associated with breeding seasons will prompt a hormonal signal for birds to begin regenerating feathers. This has been experimentally induced using thyroid hormones in the Rhode Island Red Fowls. [79]

Mammals

Spiny mice (Acomys cahirinus pictured here) can regenerate skin, cartilage, nerves and muscle. Spiny Mice.jpg
Spiny mice (Acomys cahirinus pictured here) can regenerate skin, cartilage, nerves and muscle.

Mammals are capable of cellular and physiological regeneration, but have generally poor reparative regenerative ability across the group. [1] [27] Examples of physiological regeneration in mammals include epithelial renewal (e.g., skin and intestinal tract), red blood cell replacement, antler regeneration and hair cycling. [80] [81] Male deer lose their antlers annually during the months of January to April then through regeneration are able to regrow them as an example of physiological regeneration. A deer antler is the only appendage of a mammal that can be regrown every year. [82] While reparative regeneration is a rare phenomenon in mammals, it does occur. A well-documented example is regeneration of the digit tip distal to the nail bed. [83] Reparative regeneration has also been observed in rabbits, pikas and African spiny mice. In 2012, researchers discovered that two species of African spiny mice, Acomys kempi and Acomys percivali, were capable of completely regenerating the autotomically released or otherwise damaged tissue. These species can regrow hair follicles, skin, sweat glands, fur and cartilage. [84] In addition to these two species, subsequent studies demonstrated that Acomys cahirinus could regenerate skin and excised tissue in the ear pinna. [85] [86]

Despite these examples, it is generally accepted that adult mammals have limited regenerative capacity compared to most vertebrate embryos/larvae, adult salamanders and fish. [87] But the regeneration therapy approach of Robert O. Becker, using electrical stimulation, has shown promising results for rats [88] and mammals in general. [89]

Some researchers have also claimed that the MRL mouse strain exhibits enhanced regenerative abilities. Work comparing the differential gene expression of scarless healing MRL mice and a poorly-healing C57BL/6 mouse strain, identified 36 genes differentiating the healing process between MRL mice and other mice. [90] [91] Study of the regenerative process in these animals is aimed at discovering how to duplicate them in humans, such as deactivation of the p21 gene. [92] [93] However, recent work has shown that MRL mice actually close small ear holes with scar tissue, rather than regeneration as originally claimed. [85]

MRL mice are not protected against myocardial infarction; heart regeneration in adult mammals (neocardiogenesis) is limited, because heart muscle cells are nearly all terminally differentiated. MRL mice show the same amount of cardiac injury and scar formation as normal mice after a heart attack. [94] However, recent studies provide evidence that this may not always be the case, and that MRL mice can regenerate after heart damage. [95]

Humans

The regrowth of lost tissues or organs in the human body is being researched. Some tissues such as skin regrow quite readily; others have been thought to have little or no capacity for regeneration, but ongoing research suggests that there is some hope for a variety of tissues and organs. [1] [96] Human organs that have been regenerated include the bladder, vagina and the penis. [97]

As are all metazoans, humans are capable of physiological regeneration (i.e. the replacement of cells during homeostatic maintenance that does not necessitate injury). For example, the regeneration of red blood cells via erythropoiesis occurs through the maturation of erythrocytes from hematopoietic stem cells in the bone marrow, their subsequent circulation for around 90 days in the blood stream, and their eventual cell-death in the spleen. [98] Another example of physiological regeneration is the sloughing and rebuilding of a functional endometrium during each menstrual cycle in females in response to varying levels of circulating estrogen and progesterone. [99]

However, humans are limited in their capacity for reparative regeneration, which occurs in response to injury. One of the most studied regenerative responses in humans is the hypertrophy of the liver following liver injury. [100] [101] For example, the original mass of the liver is re-established in direct proportion to the amount of liver removed following partial hepatectomy, [102] which indicates that signals from the body regulate liver mass precisely, both positively and negatively, until the desired mass is reached. This response is considered cellular regeneration (a form of compensatory hypertrophy) where the function and mass of the liver is regenerated through the proliferation of existing mature hepatic cells (mainly hepatocytes), but the exact morphology of the liver is not regained. [101] This process is driven by growth factor and cytokine regulated pathways. [100] The normal sequence of inflammation and regeneration does not function accurately in cancer. Specifically, cytokine stimulation of cells leads to expression of genes that change cellular functions and suppress the immune response. [103]

Adult neurogenesis is also a form of cellular regeneration. For example, hippocampal neuron renewal occurs in normal adult humans at an annual turnover rate of 1.75% of neurons. [104] Cardiac myocyte renewal has been found to occur in normal adult humans, [105] and at a higher rate in adults following acute heart injury such as infarction. [106] Even in adult myocardium following infarction, proliferation is only found in around 1% of myocytes around the area of injury, which is not enough to restore function of cardiac muscle. However, this may be an important target for regenerative medicine as it implies that regeneration of cardiomyocytes, and consequently of myocardium, can be induced.

Another example of reparative regeneration in humans is fingertip regeneration, which occurs after phalanx amputation distal to the nail bed (especially in children) [107] [108] and rib regeneration, which occurs following osteotomy for scoliosis treatment (though usually regeneration is only partial and may take up to one year). [109]

Yet another example of regeneration in humans is vas deferens regeneration, which occurs after a vasectomy and which results in vasectomy failure. [110]

Reptiles

The ability and degree of regeneration in reptiles differs among the various species (see [111] ), but the most notable and well-studied occurrence is tail-regeneration in lizards. [112] [113] [114] In addition to lizards, regeneration has been observed in the tails and maxillary bone of crocodiles and adult neurogenesis has also been noted. [112] [115] [116] Tail regeneration has never been observed in snakes, but see. [111] Lizards possess the highest regenerative capacity as a group. [113] [114] [117] Following autotomous tail loss, epimorphic regeneration of a new tail proceeds through a blastema-mediated process that results in a functionally and morphologically similar structure. [112] [113]

Chondrichthyes

It has been estimated that the average shark loses about 30,000 to 40,000 teeth in a lifetime. Leopard sharks routinely replace their teeth every 9–12 days and this is an example of physiological regeneration. This can occur because shark teeth are not attached to a bone, but instead are developed within a bony cavity. [74]

Rhodopsin regeneration has been studied in skates and rays. After complete photo-bleaching, rhodopsin can completely regenerate within 2 hours in the retina. [118]

White bamboo sharks can regenerate at least two-thirds of their liver and this has been linked to three micro RNAs, xtr-miR-125b, fru-miR-204, and has-miR-142-3p_R-. In one study, two-thirds of the liver was removed and within 24 hours more than half of the liver had undergone hypertrophy. [119]

Some sharks can regenerate scales and even skin following damage. Within two weeks of skin wounding, mucus is secreted into the wound and this initiates the healing process. One study showed that the majority of the wounded area was regenerated within 4 months, but the regenerated area also showed a high degree of variability. [120]

See also

Notes

  1. 1 2 3 4 Birbrair A, Zhang T, Wang ZM, Messi ML, Enikolopov GN, Mintz A, Delbono O (August 2013). "Role of pericytes in skeletal muscle regeneration and fat accumulation". Stem Cells and Development. 22 (16): 2298–314. doi:10.1089/scd.2012.0647. PMC   3730538 . PMID   23517218.
  2. 1 2 Carlson BM (2007). Principles of Regenerative Biology. Elsevier Inc. p. 400. ISBN   978-0-12-369439-3.
  3. ↑ Gabor MH, Hotchkiss RD (March 1979). "Parameters governing bacterial regeneration and genetic recombination after fusion of Bacillus subtilis protoplasts". Journal of Bacteriology. 137 (3): 1346–53. doi:10.1128/JB.137.3.1346-1353.1979. PMC   218319 . PMID   108246.
  4. ↑ Sinigaglia, Chiara; Alié, Alexandre; Tiozzo, Stefano (2022), Blanchoud, Simon; Galliot, Brigitte (eds.), "The Hazards of Regeneration: From Morgan's Legacy to Evo-Devo", Whole-Body Regeneration, vol. 2450, New York, NY: Springer US, pp. 3–25, doi:10.1007/978-1-0716-2172-1_1, ISBN   978-1-0716-2171-4, PMC   9761548 , PMID   35359300
  5. 1 2 Min S, Wang SW, Orr W (2006). "Graphic general pathology: 2.2 complete regeneration". Pathology. pathol.med.stu.edu.cn. Archived from the original on 2012-12-07. Retrieved 2012-12-07. (1) Complete regeneration: The new tissue is the same as the tissue that was lost. After the repair process has been completed, the structure and function of the injured tissue are completely normal
  6. 1 2 Min S, Wang SW, Orr W (2006). "Graphic general pathology: 2.3 Incomplete regeneration". Pathology. pathol.med.stu.edu.cn. Archived from the original on 2013-11-10. Retrieved 2012-12-07. The new tissue is not the same as the tissue that was lost. After the repair process has been completed, there is a loss in the structure or function of the injured tissue. In this type of repair, it is common that granulation tissue (stromal connective tissue) proliferates to fill the defect created by the necrotic cells. The necrotic cells are then replaced by scar tissue.
  7. ↑ Himeno Y, Engelman RW, Good RA (June 1992). "Influence of calorie restriction on oncogene expression and DNA synthesis during liver regeneration". Proceedings of the National Academy of Sciences of the United States of America. 89 (12): 5497–501. Bibcode:1992PNAS...89.5497H. doi: 10.1073/pnas.89.12.5497 . PMC   49319 . PMID   1608960.
  8. ↑ Bryant PJ, Fraser SE (May 1988). "Wound healing, cell communication, and DNA synthesis during imaginal disc regeneration in Drosophila". Developmental Biology. 127 (1): 197–208. doi:10.1016/0012-1606(88)90201-1. PMID   2452103.
  9. 1 2 Brockes JP, Kumar A (2008). "Comparative aspects of animal regeneration". Annual Review of Cell and Developmental Biology. 24: 525–49. doi:10.1146/annurev.cellbio.24.110707.175336. PMID   18598212.
  10. 1 2 Kohlsdorf, Tiana; Schneider, Igor (March 2021). "Towards an evolutionary framework for animal regeneration". Journal of Experimental Zoology Part B: Molecular and Developmental Evolution. 336 (2): 87–88. Bibcode:2021JEZB..336...87K. doi:10.1002/jez.b.23034. ISSN   1552-5007. PMID   33600616. S2CID   231963500.
  11. ↑ Tiozzo, Stefano; Copley, Richard R. (2015-06-23). "Reconsidering regeneration in metazoans: an evo-devo approach". Frontiers in Ecology and Evolution. 3. doi: 10.3389/fevo.2015.00067 . ISSN   2296-701X.
  12. 1 2 Sánchez Alvarado A (June 2000). "Regeneration in the metazoans: why does it happen?" (PDF). BioEssays. 22 (6): 578–90. doi:10.1002/(SICI)1521-1878(200006)22:6<578::AID-BIES11>3.0.CO;2-#. PMID   10842312. Archived from the original (PDF) on 2013-11-11. Retrieved 2010-12-15.
  13. 1 2 Reddien PW, Sánchez Alvarado A (2004). "Fundamentals of planarian regeneration". Annual Review of Cell and Developmental Biology. 20: 725–57. doi:10.1146/annurev.cellbio.20.010403.095114. PMID   15473858. S2CID   1320382.
  14. ↑ Campbell NA (1996). Biology (4th ed.). California: The Benjamin Cummings Publishing Company, Inc. p. 1206. ISBN   978-0-8053-1940-8.
  15. ↑ Wilkie IC (December 2001). "Autotomy as a prelude to regeneration in echinoderms". Microscopy Research and Technique. 55 (6): 369–96. doi: 10.1002/jemt.1185 . PMID   11782069. S2CID   20291486.
  16. ↑ Maiorana VC (1977). "Tail autotomy, functional conflicts and their resolution by a salamander". Nature. 2265 (5594): 533–535. Bibcode:1977Natur.265..533M. doi:10.1038/265533a0. S2CID   4219251.
  17. ↑ Maginnis TL (2006). "The costs of autotomy and regeneration in animals: a review and framework for future research". Behavioral Ecology. 7 (5): 857–872. doi: 10.1093/beheco/arl010 .
  18. ↑ Edmondson, C. H. (1935). "Autotomy and regeneration of Hawaiian starfishes" (PDF). Bishop Museum Occasional Papers. 11 (8): 3–20.
  19. ↑ "UCSB Science Line". scienceline.ucsb.edu. Retrieved 2015-11-02.
  20. ↑ Dietze MC, Clark JS (2008). "Changing the gap dynamics paradigm: Vegetative regenerative control on forest response to disturbance" (PDF). Ecological Monographs. 78 (3): 331–347. Bibcode:2008EcoM...78..331D. doi:10.1890/07-0271.1. Archived from the original (PDF) on 2010-06-10. Retrieved 2010-12-15.
  21. ↑ Bailey J, Covington WW (2002). "Evaluation ponderosa pine regeneration rates following ecological restoration treatments in northern Arizona, USA" (PDF). Forest Ecology and Management. 155 (1–3): 271–278. doi:10.1016/S0378-1127(01)00564-3. Archived from the original (PDF) on 2013-11-11. Retrieved 2011-06-25.
  22. ↑ Fu SY, Gordon T (1997). "The cellular and molecular basis of peripheral nerve regeneration". Molecular Neurobiology. 14 (1–2): 67–116. doi:10.1007/BF02740621. PMID   9170101. S2CID   13045638.
  23. ↑ Akimenko MA, Johnson SL, Westerfield M, Ekker M (February 1995). "Differential induction of four msx homeobox genes during fin development and regeneration in zebrafish" (PDF). Development. 121 (2): 347–57. doi:10.1242/dev.121.2.347. PMID   7768177.
  24. 1 2 Sánchez Alvarado A, Tsonis PA (November 2006). "Bridging the regeneration gap: genetic insights from diverse animal models" (PDF). Nature Reviews Genetics. 7 (11): 873–84. doi:10.1038/nrg1923. PMID   17047686. S2CID   2978615. Archived from the original (PDF) on 2013-11-10. Retrieved 2010-12-16.
  25. ↑ Kumar A, Godwin JW, Gates PB, Garza-Garcia AA, Brockes JP (November 2007). "Molecular basis for the nerve dependence of limb regeneration in an adult vertebrate". Science. 318 (5851): 772–7. Bibcode:2007Sci...318..772K. doi:10.1126/science.1147710. PMC   2696928 . PMID   17975060.
  26. 1 2 Skinner DM (1985). "Molting and Regneration". In Bliss DE, Mantel LH (eds.). Integument, Pigments, and Hormonal Processes. Vol. 9. Academic Press. pp. 46–146. ISBN   978-0-323-13922-9.
  27. 1 2 Seifert AW, Monaghan JR, Smith MD, Pasch B, Stier AC, Michonneau F, Maden M (May 2012). "The influence of fundamental traits on mechanisms controlling appendage regeneration". Biological Reviews of the Cambridge Philosophical Society. 87 (2): 330–45. doi:10.1111/j.1469-185X.2011.00199.x. PMID   21929739. S2CID   22877405.
  28. ↑ Travis DF (February 1955). "The Molting Cycle of the Spiny Lobster, Panulirus argus Latreille. II. Pre-Ecdysial Histological and Histochemical Changes in the Hepatopancreas and Integumental Tissues". Biological Bulletin. 108 (1): 88–112. doi:10.2307/1538400. JSTOR   1538400.
  29. ↑ Mito, Taro; Ishimaru, Yoshiyasu; Watanabe, Takahito; Nakamura, Taro; Ylla, Guillem; Noji, Sumihare; Extavour, Cassandra G. (2022), "Cricket: The third domesticated insect", Current Topics in Developmental Biology, 147, Elsevier: 291–306, doi:10.1016/bs.ctdb.2022.02.003, ISBN   978-0-12-820154-1, PMID   35337452 , retrieved 2022-06-08
  30. 1 2 3 4 Fox, Donald T.; Cohen, Erez; Smith-Bolton, Rachel (2020-04-01). "Model systems for regeneration: Drosophila". Development. 147 (7): dev173781. doi:10.1242/dev.173781. ISSN   1477-9129. PMC   7157589 . PMID   32253254.
  31. ↑ Roche, John P. (September 22, 2020). "Limb Regeneration in Lady Beetles: Product of Selection or Developmental Byproduct?". Entomology Today. Entomological Society of America. Retrieved September 23, 2020.
  32. ↑ Das S (November 2015). "Morphological, Molecular, and Hormonal Basis of Limb Regeneration across Pancrustacea". Integrative and Comparative Biology. 55 (5): 869–77. doi: 10.1093/icb/icv101 . PMID   26296354.
  33. ↑ Hamada Y, Bando T, Nakamura T, Ishimaru Y, Mito T, Noji S, Tomioka K, Ohuchi H (September 2015). "Leg regeneration is epigenetically regulated by histone H3K27 methylation in the cricket Gryllus bimaculatus". Development. 142 (17): 2916–27. doi: 10.1242/dev.122598 . PMID   26253405.
  34. ↑ Nisani Z, Dunbar SG, Hayes WK (June 2007). "Cost of venom regeneration in Parabuthus transvaalicus (Arachnida: Buthidae)". Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology. 147 (2): 509–13. doi:10.1016/j.cbpa.2007.01.027. PMID   17344080.
  35. ↑ Moya, Iván M; Halder, Georg (2016-12-01). "The Hippo pathway in cellular reprogramming and regeneration of different organs". Current Opinion in Cell Biology. Differentiation and disease. 43: 62–68. doi:10.1016/j.ceb.2016.08.004. ISSN   0955-0674. PMID   27592171.
  36. 1 2 Bely AE (August 2006). "Distribution of segment regeneration ability in the Annelida". Integrative and Comparative Biology. 46 (4): 508–18. doi: 10.1093/icb/icj051 . PMID   21672762.
  37. ↑ Hill SD (December 1972). "Caudal regeneration in the absence of a brain in two species of sedentary polychaetes". Journal of Embryology and Experimental Morphology. 28 (3): 667–80. PMID   4655324.
  38. ↑ Giani VC, Yamaguchi E, Boyle MJ, Seaver EC (May 2011). "Somatic and germline expression of piwi during development and regeneration in the marine polychaete annelid Capitella teleta". EvoDevo. 2: 10. doi: 10.1186/2041-9139-2-10 . PMC   3113731 . PMID   21545709.
  39. 1 2 3 4 5 6 Zoran MJ (2001). "Regeneration in Annelids". Encyclopedia of Life Sciences. John Wiley & Sons, Ltd. doi:10.1002/9780470015902.a0022103. ISBN   978-0-470-01590-2.
  40. ↑ Bely AE (October 2014). "Early events in annelid regeneration: a cellular perspective". Integrative and Comparative Biology. 54 (4): 688–99. doi: 10.1093/icb/icu109 . PMID   25122930.
  41. ↑ Candia Carnevali MD, Bonasoro F, Patruno M, Thorndyke MC (October 1998). "Cellular and molecular mechanisms of arm regeneration in crinoid echinoderms: the potential of arm explants". Development Genes and Evolution. 208 (8): 421–30. doi:10.1007/s004270050199. PMID   9799422. S2CID   23560812.
  42. ↑ San Miguel-Ruiz JE, Maldonado-Soto AR, García-Arrarás JE (January 2009). "Regeneration of the radial nerve cord in the sea cucumber Holothuria glaberrima". BMC Developmental Biology. 9: 3. doi: 10.1186/1471-213X-9-3 . PMC   2640377 . PMID   19126208.
  43. ↑ Patruno M, Thorndyke MC, Candia Carnevali MD, Bonasoro F, Beesley PW (March 2001). "Growth factors, heat-shock proteins and regeneration in echinoderms". The Journal of Experimental Biology. 204 (Pt 5): 843–8. doi:10.1242/jeb.204.5.843. PMID   11171408.
  44. 1 2 3 Morgan TH (1900). "Regeneration in Planarians". Archiv für Entwicklungsmechanik der Organismen. 10 (1): 58–119. doi:10.1007/BF02156347. hdl: 2027/hvd.32044107333064 . S2CID   33712732.
  45. ↑ García-Arrarás JE, Greenberg MJ (December 2001). "Visceral regeneration in holothurians". Microscopy Research and Technique. 55 (6): 438–51. doi: 10.1002/jemt.1189 . PMID   11782073. S2CID   11533400.
  46. ↑ Sánchez Alvarado A, Newmark PA (1998). "The use of planarians to dissect the molecular basis of metazoan regeneration". Wound Repair and Regeneration. 6 (4): 413–20. doi:10.1046/j.1524-475x.1998.60418.x. PMID   9824561. S2CID   8085897.
  47. 1 2 Montgomery JR, Coward SJ (July 1974). "On the minimal size of a planarian capable of regeneration". Transactions of the American Microscopical Society. 93 (3): 386–91. doi:10.2307/3225439. JSTOR   3225439. PMID   4853459.
  48. ↑ Elliott SA, Sánchez Alvarado A (2012). "The history and enduring contributions of planarians to the study of animal regeneration". Wiley Interdisciplinary Reviews: Developmental Biology. 2 (3): 301–26. doi:10.1002/wdev.82. PMC   3694279 . PMID   23799578.
  49. ↑ Wagner DE, Wang IE, Reddien PW (May 2011). "Clonogenic neoblasts are pluripotent adult stem cells that underlie planarian regeneration". Science. 332 (6031): 811–6. Bibcode:2011Sci...332..811W. doi:10.1126/science.1203983. PMC   3338249 . PMID   21566185.
  50. 1 2 Holland, Nicholas (2021), "Vicenzo Colucci's 1886 memoir, Intorno alla rigenerazione degli arti e della coda nei tritoni, annotated and translated into English as: Concerning regeneration of the limbs and tail in salamanders", The European Zoological Journal, 88: 837–890, doi: 10.1080/24750263.2021.1943549
  51. 1 2 Brockes JP, Kumar A, Velloso CP (2001). "Regeneration as an evolutionary variable". Journal of Anatomy. 199 (Pt 1–2): 3–11. doi:10.1046/j.1469-7580.2001.19910003.x. PMC   1594962 . PMID   11523827.
  52. ↑ Brockes JP, Kumar A (August 2002). "Plasticity and reprogramming of differentiated cells in amphibian regeneration". Nature Reviews Molecular Cell Biology. 3 (8): 566–74. doi:10.1038/nrm881. PMID   12154368. S2CID   21409289.
  53. ↑ Iten LE, Bryant SV (December 1973). "Forelimb regeneration from different levels of amputation in the newt, Notophthalmus viridescens: Length, rate, and stages". Wilhelm Roux' Archiv für Entwicklungsmechanik der Organismen. 173 (4): 263–282. doi:10.1007/BF00575834. PMID   28304797. S2CID   3946430.
  54. 1 2 Endo T, Bryant SV, Gardiner DM (June 2004). "A stepwise model system for limb regeneration" (PDF). Developmental Biology. 270 (1): 135–45. doi:10.1016/j.ydbio.2004.02.016. PMID   15136146. S2CID   7581434.
  55. ↑ Satoh A, Bryant SV, Gardiner DM (June 2012). "Nerve signaling regulates basal keratinocyte proliferation in the blastema apical epithelial cap in the axolotl (Ambystoma mexicanum)". Developmental Biology. 366 (2): 374–81. doi: 10.1016/j.ydbio.2012.03.022 . PMID   22537500.
  56. ↑ Christensen RN, Tassava RA (February 2000). "Apical epithelial cap morphology and fibronectin gene expression in regenerating axolotl limbs". Developmental Dynamics. 217 (2): 216–24. doi:10.1002/(sici)1097-0177(200002)217:2<216::aid-dvdy8>3.0.co;2-8. PMID   10706145. S2CID   29415248.
  57. 1 2 Bryant SV, Endo T, Gardiner DM (2002). "Vertebrate limb regeneration and the origin of limb stem cells". The International Journal of Developmental Biology. 46 (7): 887–96. PMID   12455626.
  58. ↑ Mullen LM, Bryant SV, Torok MA, Blumberg B, Gardiner DM (November 1996). "Nerve dependency of regeneration: the role of Distal-less and FGF signaling in amphibian limb regeneration". Development. 122 (11): 3487–97. doi:10.1242/dev.122.11.3487. PMID   8951064.
  59. ↑ Souppouris, Aaron (May 23, 2013). "Scientists identify cell that could hold the secret to limb regeneration". The Verge. Macrophages are a type of repairing cell that devour dead cells and pathogens, and trigger other immune cells to respond to pathogens.
  60. ↑ Godwin JW, Pinto AR, Rosenthal NA (June 2013). "Macrophages are required for adult salamander limb regeneration". Proceedings of the National Academy of Sciences of the United States of America. 110 (23): 9415–20. Bibcode:2013PNAS..110.9415G. doi: 10.1073/pnas.1300290110 . PMC   3677454 . PMID   23690624.
  61. ↑ Min S, Whited JL. Limb blastema formation: How much do we know at a genetic and epigenetic level? J Biol Chem. 2023 Feb;299(2):102858. doi: 10.1016/j.jbc.2022.102858. Epub 2022 Dec 31. PMID 36596359; PMCID: PMC9898764
  62. ↑ Voss SR, Muzinic L, Zimmerman G (2018). "Sal-Site". Ambystoma.org.
  63. ↑ "Single-cell Stereo-seq reveals new insights into axolotl brain regeneration". News-Medical.net. 6 September 2022. Retrieved 19 October 2022.
  64. ↑ Wei, Xiaoyu; Fu, Sulei; Li, Hanbo; Liu, Yang; Wang, Shuai; Feng, Weimin; Yang, Yunzhi; Liu, Xiawei; Zeng, Yan-Yun; Cheng, Mengnan; Lai, Yiwei; Qiu, Xiaojie; Wu, Liang; Zhang, Nannan; Jiang, Yujia; Xu, Jiangshan; Su, Xiaoshan; Peng, Cheng; Han, Lei; Lou, Wilson Pak-Kin; Liu, Chuanyu; Yuan, Yue; Ma, Kailong; Yang, Tao; Pan, Xiangyu; Gao, Shang; Chen, Ao; Esteban, Miguel A.; Yang, Huanming; Wang, Jian; Fan, Guangyi; Liu, Longqi; Chen, Liang; Xu, Xun; Fei, Ji-Feng; Gu, Ying (2 September 2022). "Single-cell Stereo-seq reveals induced progenitor cells involved in axolotl brain regeneration" . Science. 377 (6610): eabp9444. doi:10.1126/science.abp9444. ISSN   0036-8075. PMID   36048929. S2CID   252010604.
  65. 1 2 Liversage RA, Anderson MJ, Korneluk RG (February 2005). "Regenerative response of amputated forelimbs of Xenopus laevis froglets to partial denervation". Journal of Morphology. 191 (2): 131–144. doi:10.1002/jmor.1051910204. PMID   29921109. S2CID   49315283.
  66. 1 2 Reya T, Clevers H (April 2005). "Wnt signalling in stem cells and cancer". Nature. 434 (7035): 843–50. Bibcode:2005Natur.434..843R. doi:10.1038/nature03319. PMID   15829953. S2CID   3645313.
  67. ↑ Murugan, Nirosha J.; Vigran, Hannah J.; Miller, Kelsie A.; Golding, Annie; Pham, Quang L.; Sperry, Megan M.; Rasmussen-Ivey, Cody; Kane, Anna W.; Kaplan, David L.; Levin, Michael (28 January 2022). "Acute multidrug delivery via a wearable bioreactor facilitates long-term limb regeneration and functional recovery in adult Xenopus laevis". Science Advances. 8 (4): eabj2164. Bibcode:2022SciA....8.2164M. doi: 10.1126/sciadv.abj2164 . PMC   8791464 . PMID   35080969.
  68. 1 2 3 4 5 Bosch TC (March 2007). "Why polyps regenerate and we don't: towards a cellular and molecular framework for Hydra regeneration". Developmental Biology. 303 (2): 421–33. doi: 10.1016/j.ydbio.2006.12.012 . PMID   17234176.
  69. 1 2 3 4 Wenger Y, Buzgariu W, Reiter S, Galliot B (August 2014). "Injury-induced immune responses in Hydra". Seminars in Immunology. 26 (4): 277–94. doi: 10.1016/j.smim.2014.06.004 . PMID   25086685.
  70. ↑ Buzgariu W, Crescenzi M, Galliot B (2014). "Robust G2 pausing of adult stem cells in Hydra". Differentiation; Research in Biological Diversity. 87 (1–2). Science Direct: 83–99. doi: 10.1016/j.diff.2014.03.001 . PMID   24703763.
  71. ↑ Morgan TH (1901). Regeneration. Columbia University Biological Series. Vol. 7. New York: The MacMillan Company.
  72. ↑ Agata K, Saito Y, Nakajima E (February 2007). "Unifying principles of regeneration I: Epimorphosis versus morphallaxis". Development, Growth & Differentiation. 49 (2): 73–8. doi: 10.1111/j.1440-169X.2007.00919.x . PMID   17335428. S2CID   29433846.
  73. 1 2 Murad R, Macias-Muñoz A, Wong A, Ma X, Mortazavi A. Coordinated Gene Expression and Chromatin Regulation during Hydra Head Regeneration. Genome Biol Evol. 2021 Dec 1;13(12):evab221. doi: 10.1093/gbe/evab221. PMID 34877597; PMCID: PMC8651858
  74. 1 2 3 Vorontsova MA, Liosner LD (1960). Billet F (ed.). Asexual Reproduction and Regeneration. Translated by Allen PM. London: Pergamon Press. pp. 367–371.
  75. ↑ Sidorova VF (July 1962). "Liver regeneration in birds". Biulleten' Eksperimental'noi Biologii I Meditsiny. 52 (6): 1426–9. doi:10.1007/BF00785312. PMID   14039265. S2CID   39410595.
  76. ↑ Cotanche DA, Lee KH, Stone JS, Picard DA (January 1994). "Hair cell regeneration in the bird cochlea following noise damage or ototoxic drug damage". Anatomy and Embryology. 189 (1): 1–18. doi:10.1007/BF00193125. PMID   8192233. S2CID   25619337.
  77. ↑ Coleman CM (September 2008). "Chicken embryo as a model for regenerative medicine". Birth Defects Research. Part C, Embryo Today. 84 (3): 245–56. doi:10.1002/bdrc.20133. PMID   18773459.
  78. ↑ Özpolat BD, Zapata M, Daniel Frugé J, Coote J, Lee J, Muneoka K, Anderson R (December 2012). "Regeneration of the elbow joint in the developing chick embryo recapitulates development". Developmental Biology. 372 (2): 229–38. doi:10.1016/j.ydbio.2012.09.020. PMC   3501998 . PMID   23036343.
  79. ↑ Hosker A (1936). "Regeneration of Feathers after Thyroid Feeding". Journal of Experimental Biology. 13 (3): 344–351. doi: 10.1242/jeb.13.3.344 .
  80. ↑ Kresie L (April 2001). "Artificial blood: an update on current red cell and platelet substitutes". Proceedings. 14 (2): 158–61. doi:10.1080/08998280.2001.11927754. PMC   1291332 . PMID   16369608.
  81. ↑ Li C, Pearson A, McMahon C (2013). "Morphogenetic mechanisms in the cyclic regeneration of hair follicles and deer antlers from stem cells". BioMed Research International. 2013: 643601. doi: 10.1155/2013/643601 . PMC   3870647 . PMID   24383056.
  82. ↑ Price J, Allen S (May 2004). "Exploring the mechanisms regulating regeneration of deer antlers". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 359 (1445): 809–22. doi:10.1098/rstb.2004.1471. PMC   1693364 . PMID   15293809.
  83. ↑ Fernando WA, Leininger E, Simkin J, Li N, Malcom CA, Sathyamoorthi S, Han M, Muneoka K (February 2011). "Wound healing and blastema formation in regenerating digit tips of adult mice". Developmental Biology. 350 (2): 301–10. doi:10.1016/j.ydbio.2010.11.035. PMC   3031655 . PMID   21145316.
  84. ↑ Seifert AW, Kiama SG, Seifert MG, Goheen JR, Palmer TM, Maden M (September 2012). "Skin shedding and tissue regeneration in African spiny mice (Acomys)". Nature. 489 (7417): 561–5. Bibcode:2012Natur.489..561S. doi:10.1038/nature11499. PMC   3480082 . PMID   23018966.
  85. 1 2 Gawriluk TR, Simkin J, Thompson KL, Biswas SK, Clare-Salzler Z, Kimani JM, Kiama SG, Smith JJ, Ezenwa VO, Seifert AW (April 2016). "Comparative analysis of ear-hole closure identifies epimorphic regeneration as a discrete trait in mammals". Nature Communications. 7: 11164. Bibcode:2016NatCo...711164G. doi:10.1038/ncomms11164. PMC   4848467 . PMID   27109826.
  86. ↑ Matias Santos D, Rita AM, Casanellas I, Brito Ova A, Araújo IM, Power D, Tiscornia G (February 2016). "Ear wound regeneration in the African spiny mouse Acomys cahirinus". Regeneration. 3 (1): 52–61. doi:10.1002/reg2.50. PMC   4857749 . PMID   27499879.
  87. ↑ Xu K (July 2013). "Humans' Ability To Regenerate Damaged Organs Is At Our Fingertips". Business Insider.
  88. ↑ Becker RO (January 1972). "Stimulation of partial limb regeneration in rats". Nature. 235 (5333): 109–11. Bibcode:1972Natur.235..109B. doi:10.1038/235109a0. PMID   4550399. S2CID   4209650.
  89. ↑ Becker RO, Spadaro JA (May 1972). "Electrical stimulation of partial limb regeneration in mammals". Bulletin of the New York Academy of Medicine. 48 (4): 627–41. PMC   1806700 . PMID   4503923.
  90. ↑ Masinde G, Li X, Baylink DJ, Nguyen B, Mohan S (April 2005). "Isolation of wound healing/regeneration genes using restrictive fragment differential display-PCR in MRL/MPJ and C57BL/6 mice". Biochemical and Biophysical Research Communications. 330 (1): 117–22. doi:10.1016/j.bbrc.2005.02.143. PMID   15781240.
  91. ↑ Hayashi ML, Rao BS, Seo JS, Choi HS, Dolan BM, Choi SY, Chattarji S, Tonegawa S (July 2007). "Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice". Proceedings of the National Academy of Sciences of the United States of America. 104 (27): 11489–94. Bibcode:2007PNAS..10411489H. doi: 10.1073/pnas.0705003104 . PMC   1899186 . PMID   17592139.
  92. ↑ Bedelbaeva K, Snyder A, Gourevitch D, Clark L, Zhang XM, Leferovich J, Cheverud JM, Lieberman P, Heber-Katz E (March 2010). "Lack of p21 expression links cell cycle control and appendage regeneration in mice". Proceedings of the National Academy of Sciences of the United States of America. 107 (13): 5845–50. Bibcode:2010PNAS..107.5845B. doi: 10.1073/pnas.1000830107 . PMC   2851923 . PMID   20231440.
  93. ↑ Humans Could Regenerate Tissue Like Newts By Switching Off a Single Gene
  94. ↑ Abdullah I, Lepore JJ, Epstein JA, Parmacek MS, Gruber PJ (March–April 2005). "MRL mice fail to heal the heart in response to ischemia-reperfusion injury". Wound Repair and Regeneration. 13 (2): 205–8. doi:10.1111/j.1067-1927.2005.130212.x. PMID   15828946. S2CID   7360046.
  95. ↑ "Regeneration in the mammalian heart demonstrated by Wistar researchers | EurekAlert! Science News". Eurekalert.org. Retrieved 2019-03-16.
  96. ↑ Min S, Wang SW, Orr W (2006). "Graphic general pathology: 2.2 complete regeneration". Pathology. pathol.med.stu.edu.cn. Archived from the original on 2012-12-07. Retrieved 2013-11-10. After the repair process has been completed, the structure and function of the injured tissue are completely normal. This type of regeneration is common in physiological situations. Examples of physiological regeneration are the continual replacement of cells of the skin and repair of the endometrium after menstruation. Complete regeneration can occur in pathological situations in tissues that have good regenerative capacity.
  97. ↑ Mohammadi D (4 October 2014). "Bioengineered organs: The story so far…". The Guardian. Retrieved 9 March 2015.
  98. ↑ Carlson BM (2007). Principles of Regenerative Biology . Academic Press. pp.  25–26. ISBN   978-0-12-369439-3.
  99. ↑ Ferenczy A, Bertrand G, Gelfand MM (April 1979). "Proliferation kinetics of human endometrium during the normal menstrual cycle". American Journal of Obstetrics and Gynecology. 133 (8): 859–67. doi:10.1016/0002-9378(79)90302-8. PMID   434029.
  100. 1 2 Michalopoulos GK, DeFrances MC (April 1997). "Liver regeneration". Science. 276 (5309): 60–6. doi:10.1126/science.276.5309.60. PMID   9082986. S2CID   2756510.
  101. 1 2 Taub R (October 2004). "Liver regeneration: from myth to mechanism". Nature Reviews Molecular Cell Biology. 5 (10): 836–47. doi:10.1038/nrm1489. PMID   15459664. S2CID   30647609.
  102. ↑ Kawasaki S, Makuuchi M, Ishizone S, Matsunami H, Terada M, Kawarazaki H (March 1992). "Liver regeneration in recipients and donors after transplantation". Lancet. 339 (8793): 580–1. doi:10.1016/0140-6736(92)90867-3. PMID   1347095. S2CID   34148354.
  103. ↑ Vlahopoulos SA (August 2017). "Aberrant control of NF-κB in cancer permits transcriptional and phenotypic plasticity, to curtail dependence on host tissue: molecular mode". Cancer Biology & Medicine. 14 (3): 254–270. doi:10.20892/j.issn.2095-3941.2017.0029. PMC   5570602 . PMID   28884042.
  104. ↑ Spalding KL, Bergmann O, Alkass K, Bernard S, Salehpour M, Huttner HB, Boström E, Westerlund I, Vial C, Buchholz BA, Possnert G, Mash DC, Druid H, Frisén J (June 2013). "Dynamics of hippocampal neurogenesis in adult humans". Cell. 153 (6): 1219–1227. doi:10.1016/j.cell.2013.05.002. PMC   4394608 . PMID   23746839.
  105. ↑ Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisén J (April 2009). "Evidence for cardiomyocyte renewal in humans". Science. 324 (5923): 98–102. Bibcode:2009Sci...324...98B. doi:10.1126/science.1164680. PMC   2991140 . PMID   19342590.
  106. ↑ Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R, Nadal-Ginard B, Silvestri F, Leri A, Beltrami CA, Anversa P (June 2001). "Evidence that human cardiac myocytes divide after myocardial infarction". The New England Journal of Medicine. 344 (23): 1750–7. doi: 10.1056/NEJM200106073442303 . PMID   11396441. (This paper currently has an expression of concern, see doi:10.1056/NEJMe1813801, PMID   30332558 . If this is an intentional citation to a such a paper, please replace {{ expression of concern |...}} with {{ expression of concern |...|intentional=yes}}.)
  107. ↑ McKim LH (May 1932). "Regeneration of the distal phalanx". Canadian Medical Association Journal. 26 (5): 549–50. PMC   402335 . PMID   20318716.
  108. ↑ Muneoka K, Allan CH, Yang X, Lee J, Han M (December 2008). "Mammalian regeneration and regenerative medicine". Birth Defects Research. Part C, Embryo Today. 84 (4): 265–80. doi:10.1002/bdrc.20137. PMID   19067422.
  109. ↑ Philip SJ, Kumar RJ, Menon KV (October 2005). "Morphological study of rib regeneration following costectomy in adolescent idiopathic scoliosis". European Spine Journal. 14 (8): 772–6. doi:10.1007/s00586-005-0949-8. PMC   3489251 . PMID   16047208.
  110. ↑ Korin Miller (September 11, 2017). "Here's What Happens When a Vasectomy Fails". SELF. Retrieved 2019-03-16.
  111. 1 2 Alibardi A, Meyer-Rochow VB (2021). "Regeneration in reptiles generally and the New Zealand tuatara in particular as a model to analyze organ regrowth in amniotes: A Review". Journal of Developmental Biology. 9 (3): 36. doi: 10.3390/jdb9030036 . PMC   8482124 . PMID   34564085.
  112. 1 2 3 Alibardi L (2010). "Regeneration in Reptiles and Its Position Among Vertebrates". Morphological and Cellular Aspects of Tail and Limb Regeneration in Lizards. Advances in Anatomy, Embryology and Cell Biology. Vol. 207. Heidelberg: Springer. pp. iii, v–x, 1–109. doi:10.1007/978-3-642-03733-7_1. ISBN   978-3-642-03732-0. PMID   20334040.
  113. 1 2 3 McLean KE, Vickaryous MK (August 2011). "A novel amniote model of epimorphic regeneration: the leopard gecko, Eublepharis macularius". BMC Developmental Biology. 11 (1): 50. doi: 10.1186/1471-213x-11-50 . PMC   3180301 . PMID   21846350.
  114. 1 2 Bellairs A, Bryant S (1985). "Autonomy and Regeneration in Reptiles". In Gans C, Billet F (eds.). Biology of the Reptilia. Vol. 15. New York: John Wiley and Sons. pp. 301–410.
  115. ↑ Brazaitis P (July 31, 1981). "Maxillary Regeneration in a Marsh Crocodile, Crocodylus palustris". Journal of Herpetology. 15 (3): 360–362. doi:10.2307/1563441. JSTOR   1563441.
  116. ↑ Font E, Desfilis E, Pérez-Cañellas MM, García-Verdugo JM (2001). "Neurogenesis and neuronal regeneration in the adult reptilian brain". Brain, Behavior and Evolution. 58 (5): 276–95. doi:10.1159/000057570. PMID   11978946. S2CID   1079753.
  117. ↑ Vickaryous M (2014). "Vickaryous Lab: Regeneration - Evolution - Development". Department of Biomedical Sciences, University of Guelph.
  118. ↑ Sun Y, Ripps H (November 1992). "Rhodopsin regeneration in the normal and in the detached/replaced retina of the skate". Experimental Eye Research. 55 (5): 679–89. doi:10.1016/0014-4835(92)90173-p. PMID   1478278.
  119. ↑ Lu C, Zhang J, Nie Z, Chen J, Zhang W, Ren X, Yu W, Liu L, Jiang C, Zhang Y, Guo J, Wu W, Shu J, Lv Z (2013). "Study of microRNAs related to the liver regeneration of the whitespotted bamboo shark, Chiloscyllium plagiosum". BioMed Research International. 2013: 795676. doi: 10.1155/2013/795676 . PMC   3789328 . PMID   24151623.
  120. ↑ Reif WE (June 1978). "Wound Healing in Sharks". Zoomorphology. 90 (2): 101–111. doi:10.1007/bf02568678. S2CID   29300907.

Sources

Further reading

Related Research Articles

Developmental biology is the study of the process by which animals and plants grow and develop. Developmental biology also encompasses the biology of regeneration, asexual reproduction, metamorphosis, and the growth and differentiation of stem cells in the adult organism.

Transdifferentiation, also known as lineage reprogramming, is the process in which one mature somatic cell is transformed into another mature somatic cell without undergoing an intermediate pluripotent state or progenitor cell type. It is a type of metaplasia, which includes all cell fate switches, including the interconversion of stem cells. Current uses of transdifferentiation include disease modeling and drug discovery and in the future may include gene therapy and regenerative medicine. The term 'transdifferentiation' was originally coined by Selman and Kafatos in 1974 to describe a change in cell properties as cuticle producing cells became salt-secreting cells in silk moths undergoing metamorphosis.

<span class="mw-page-title-main">Axolotl</span> Species of salamander

The axolotl is a paedomorphic salamander closely related to the tiger salamander. It is unusual among amphibians in that it reaches adulthood without undergoing metamorphosis. Instead of taking to the land, adults remain aquatic and gilled. The species was originally found in several lakes underlying what is now Mexico City, such as Lake Xochimilco and Lake Chalco. These lakes were drained by Spanish settlers after the conquest of the Aztec Empire, leading to the destruction of much of the axolotl's natural habitat.

<span class="mw-page-title-main">Planarian</span> Flatworms of the Turbellaria class

Planarians (triclads) are free-living flatworms of the class Turbellaria, order Tricladida, which includes hundreds of species, found in freshwater, marine, and terrestrial habitats. Planarians are characterized by a three-branched intestine, including a single anterior and two posterior branches. Their body is populated by adult stem cells called neoblasts, which planarians use for regenerating missing body parts. Many species are able to regenerate any missing organ, which has made planarians a popular model in research of regeneration and stem cell biology. The genome sequences of several species are available, as are tools for molecular biology analysis.

Morphallaxis is the regeneration of specific tissue in a variety of organisms due to loss or death of the existing tissue. The word comes from the Greek allazein, (αλλάζειν) which means to change.

<span class="mw-page-title-main">Blastema</span> Mass of cells capable of enacting growth and regeneration

A blastema is a mass of cells capable of growth and regeneration into organs or body parts. The changing definition of the word "blastema" has been reviewed by Holland (2021). A broad survey of how blastema has been used over time brings to light a somewhat involved history. The word entered the biomedical vocabulary in 1799 to designate a sinister acellular slime that was the starting point for the growth of cancers, themselves, at the time, thought to be acellular, as reviewed by Hajdu. Then, during the early nineteenth century, the definition broadened to include growth zones in healthy, normally developing plant and animal embryos. Contemporaneously, cancer specialists dropped the term from their vocabulary, perhaps because they felt a term connoting a state of health and normalcy was not appropriate for describing a pathological condition. During the middle decades of the nineteenth century, Schleiden and Schwann proposed the cell theory, and Remak and Virchow insisted that cells can only be generated by division of existing ones. Consequently, the conception of the blastema changed from acellular to cellular. More specifically, the term came to designate a population of embryonic cells that gave rise to a particular tissue. In short, the term blastema started being used to refer to what modern embryologists increasingly began calling a rudiment or Anlage. Importantly, the term blastema did not yet refer to a mass of undifferentiated-looking cells that accumulates relatively early in a regenerating body part. For instance, Morgan (1900), does not use the term even once in his classic book, “Regeneration.” It was not until the eve of World War 1 that Fritsch introduced the term blastema in the modern sense, as now used by contemporary students of regeneration. Currently, the old usage of blastema to refer to a normal embryological rudiment has largely disappeared.

<span class="mw-page-title-main">GDF11</span> Protein-coding gene in humans

Growth differentiation factor 11 (GDF11), also known as bone morphogenetic protein 11 (BMP-11), is a protein that in humans is encoded by the growth differentiation factor 11 gene. GDF11 is a member of the Transforming growth factor beta family.

<span class="mw-page-title-main">LIN28</span>

Lin-28 homolog A is a protein that in humans is encoded by the LIN28 gene.

<span class="mw-page-title-main">Genetically modified animal</span> Animal that has been genetically modified

Genetically modified animals are animals that have been genetically modified for a variety of purposes including producing drugs, enhancing yields, increasing resistance to disease, etc. The vast majority of genetically modified animals are at the research stage while the number close to entering the market remains small.

<span class="mw-page-title-main">FOXA2</span> Mammalian protein found in Homo sapiens

Forkhead box protein A2 (FOXA2), also known as hepatocyte nuclear factor 3-beta (HNF-3B), is a transcription factor that plays an important role during development, in mature tissues and, when dysregulated or mutated, also in cancer.

Epimorphosis is defined as the regeneration of a specific part of an organism in a way that involves extensive cell proliferation of somatic stem cells, dedifferentiation, and reformation, as well as blastema formation. Epimorphosis can be considered a simple model for development, though it only occurs in tissues surrounding the site of injury rather than occurring system-wide. Epimorphosis restores the anatomy of the organism and the original polarity that existed before the destruction of the tissue and/or a structure of the organism. Epimorphosis regeneration can be observed in both vertebrates and invertebrates such as the common examples: salamanders, annelids, and planarians.

<span class="mw-page-title-main">Betty Hay</span> Cell biologist and Developmental biologist

Elizabeth Dexter "Betty" Hay was an American cell and developmental biologist. She was best known for her research in limb regeneration, the role of the extracellular matrix (ECM) in cell differentiation, and epithelial-mesenchymal transitions (EMT). Hay led many research teams in discovering new findings in these related fields, which led her to obtain several high honors and awards for her work. Hay primarily worked with amphibians during her years of limb regeneration work and then moved onto avian epithelia for research on the ECM and EMT. Hay was thrilled by the introduction of transmission electron microscopy (TEM) during her lifetime, which aided her in many of her findings throughout her career. Moreover, Hay was a huge advocate of women in science during her lifetime.

Regeneration in humans is the regrowth of lost tissues or organs in response to injury. This is in contrast to wound healing, or partial regeneration, which involves closing up the injury site with some gradation of scar tissue. Some tissues such as skin, the vas deferens, and large organs including the liver can regrow quite readily, while others have been thought to have little or no capacity for regeneration following an injury.

<span class="mw-page-title-main">Hox genes in amphibians and reptiles</span>

Hox genes play a massive role in some amphibians and reptiles in their ability to regenerate lost limbs, especially HoxA and HoxD genes.

Scar free healing is the process by which significant injuries can heal without permanent damage to the tissue the injury has affected. In most healing, scars form due to the fibrosis and wound contraction, however in scar free healing, tissue is completely regenerated. During the 1990s, published research on the subject increased; it is a relatively recent term in the literature. Scar free healing occurs in foetal life but the ability progressively diminishes into adulthood. In other animals such as amphibians, however, tissue regeneration occurs, for example as skin regeneration in the adult axolotl.

<span class="mw-page-title-main">Developmental bioelectricity</span> Electric current produced in living cells

Developmental bioelectricity is the regulation of cell, tissue, and organ-level patterning and behavior by electrical signals during the development of embryonic animals and plants. The charge carrier in developmental bioelectricity is the ion rather than the electron, and an electric current and field is generated whenever a net ion flux occurs. Cells and tissues of all types use flows of ions to communicate electrically. Endogenous electric currents and fields, ion fluxes, and differences in resting potential across tissues comprise a signalling system. It functions along with biochemical factors, transcriptional networks, and other physical forces to regulate cell behaviour and large-scale patterning in processes such as embryogenesis, regeneration, and cancer suppression.

<span class="mw-page-title-main">Starfish regeneration</span> Star-shaped organisms

Starfish, or sea stars, are radially symmetrical, star-shaped organisms of the phylum Echinodermata and the class Asteroidea. Aside from their distinguishing shape, starfish are most recognized for their remarkable ability to regenerate, or regrow, arms and, in some cases, entire bodies. While most species require the central body to be intact in order to regenerate arms, a few tropical species can grow an entirely new starfish from just a portion of a severed limb. Starfish regeneration across species follows a common three-phase model and can take up to a year or longer to complete. Though regeneration is used to recover limbs eaten or removed by predators, starfish are also capable of autotomizing and regenerating limbs to evade predators and reproduce.

Dedifferentiation is a transient process by which cells become less specialized and return to an earlier cell state within the same lineage. This suggests an increase in cell potency, meaning that, following dedifferentiation, a cell may possess the ability to re-differentiate into more cell types than it did before dedifferentiation. This is in contrast to differentiation, where differences in gene expression, morphology, or physiology arise in a cell, making its function increasingly specialized.

<span class="mw-page-title-main">Neoblast</span> Planarian regeneration proliferative cells

Neoblasts (ˈniːəʊˌblæst) are adult stem cells found in planarian flatworms. They are the only dividing planarian cells, and they produce all cell types, including the germline. Neoblasts are abundant in the planarian parenchyma, and comprise up to 30 percent of all cells. Following injury, neoblasts rapidly divide and generate new cells, which allows planarians to regenerate any missing tissue.

Immune system contribution to regeneration of tissues generally involves specific cellular components, transcription of a wide variety of genes, morphogenesis, epithelia renewal and proliferation of damaged cell types. However, current knowledge reveals more and more studies about immune system influence that cannot be omitted. As the immune system exhibits inhibitory or inflammatory functions during regeneration, the therapies are focused on either stopping these processes or control the immune cells setting in a regenerative way, suggesting that interplay between damaged tissue and immune system response must be well-balanced. Recent studies provide evidence that immune components are required not only after body injury but also in homeostasis or senescent cells replacement.

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