Regeneration in humans

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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.


Numerous tissues and organs have been induced to regenerate. Bladders have been 3d printed in the lab since 1999. Skin tissue can be regenerated in vivo, and in vitro. Other organs and body parts that have been procured to regenerate include: penis, fats, vagina, brain tissue, thymus, and a scaled down human heart. Ongoing research, aims to induce full regeneration in more human organs.

There are various techniques that can induce regeneration. By 2016 regeneration of tissue had been induced and operationalized by science, by using four main techniques: regeneration by instrument; [1] regeneration by materials; [2] [3] regeneration by drugs [4] [5] [6] and regeneration by in vitro 3d printing. [3]

History of human tissue

In humans with non-injured tissues, the tissue is naturally regenerated over time; by default these tissues have new cells available to replace expended cells. For example, the body regenerates a full bone within 10 years, while non-injured skin tissue is regenerated within two weeks. [2] With injured tissue, the body usually has a different response – this emergency response usually involves building a degree of scar tissue over a time period longer than a regenerative response, as has been proven clinically [7] and via observation. There are many more historical and nuanced understandings about regeneration processes. In full thickness wounds that are under 2mm, regeneration generally occurs before scarring. [8] In 2008, in full thickness wounds over 3mm, it was found that a wound needed a material inserted in order to induce full tissue regeneration. [9] [10]

There are some human organs and tissues that regenerate rather than simply scar, as a result of injury. These include the liver, fingertips, and endometrium. More information is now known regarding the passive replacement of tissues in the human body, as well as the mechanics of stem cells. Advances in research have enabled the induced regeneration of many more tissues and organs than previously thought possible. The aim for these techniques is to use these techniques in the near future for the purpose of regenerating any tissue type in the human body.

History of regeneration techniques

Regenerating a human ear using a scaffold Earproject - 2x3 (6127848729).jpg
Regenerating a human ear using a scaffold

By 2016, regeneration had been operationalised and induced by four main techniques: regeneration by instrument; [1] regeneration by materials; [2] [3] regeneration by 3d printing; [3] and regeneration by drugs. [4] [5] [6] By 2016, regeneration by instrument, regeneration by materials and by regeneration drugs had been generally operationalised in vivo (inside living tissues). Whilst by 2016, regeneration by 3d printing had been generally operationalised by in vitro (inside the lab) in order to be built and prepare tissue for transplantation. [3]

Regeneration by instrument

A cut by a knife or a scalpel generally scars, though a piercing by a needle does not. [1] [11] In 1976, a 3 by 3cm scar on a non-diabetic was regenerated by insulin injections and the researchers, highlighting earlier research, argued that the insulin was regenerating the tissue. [4] [5] The anecdotal evidence also highlighted that a syringe was one of two variables that helped bring regeneration of the arm scar. [4] The syringe was injected into the four quadrants three times a day for eighty-two days. [4] After eighty-two days, after many consecutive injections, the scar was resolved and it was noted no scar was observable by the human eye. [4] After seven months the area was checked again and it was once again noted that no scar could be seen. [4]

In 1997, it was proven that wounds created with an instrument that are under 2mm can heal scar free, [8] but larger wounds that are larger than 2mm healed with a scar. [8]

In 2013 it was proven in pig tissue that full thickness micro columns of tissue, less than 0.5mm in diameter could be removed and that the replacement tissue, was regenerative tissue, not scar. The tissue was removed in a fractional pattern, with over 40% of a square area removed; and all of the fractional full thickness holes in the square area healed without scarring. [12] In 2016 this fractional pattern technique was also proven in human tissue. [1]

Regeneration with materials

Generally, humans can regenerate injured tissues in vivo for limited distances of up to 2mm. The further the wound distance is from 2mm the more the wound regeneration will need inducement. By 2009, via the use of materials, a max induced regeneration could be achieved inside a 1 cm tissue rupture. [2] Bridging the wound, the material allowed cells to cross the wound gap; the material then degraded. This technology was first used inside a broken urethra in 1996. [2] [3] In 2012, using materials, a full urethra was restored in vivo. [3]

Macrophage polarization is a strategy for skin regeneration. [13] Macrophages are differentiated from circulating monocytes. [13] Macrophages display a range of phenotypes varying from the M1, pro-inflammatory type to the M2, pro-regenerative type. [13] Material hydrogels polarise macrophages into the key M2 regenerative phenotype in vitro. [13] In 2017 hydrogels provided full regeneration of skin, with hair follicles, after partial excision of scars in pigs and after full thickness wound incisions in pigs. [13]

Regeneration by 3D printing

In 2009, the regeneration of hollow organs and tissues with a long diffusion distance, was a little more challenging. Therefore, to regenerate hollow organs and tissues with a long diffusion distance, the tissue had to be regenerated inside the lab, via the use of a 3D printer. [2]

Various tissues that have been regenerated by in vitro 3d printing include:

  • The first organ ever induced and made in the lab was the bladder, which was created in 1999. [14]
  • By 2014, there had been various tissues regenerated by the 3d printer and these tissues included: muscle, vagina, penis and the thymus.
  • In 2014, a conceptual human lung was first bioengineered in the lab. [15] [16] In 2015, the lab robustly tested its technique and regenerated a pig lung. [15] [16] The pig lung was then successfully transplanted into a pig without the use of immunosuppressive drugs. [15] [16]
  • In 2015 researchers developed a proof of principle biolimb inside a laboratory; they also estimated that it would be at least a decade for any testing of limbs in humans. The limb demonstrated fully functioning skin, muscles, blood vessels and bones. [17]
  • In April 2019 researchers 3d printed a human heart. [18] The prototype heart was made by human stem cells but only to the size of a rabbit's heart. [18] In 2019, the researchers hoped to one day place a scaled up version of the heart inside humans. [18]
Gradations of complexity
Level 1Level 2Level 3Level 4
SkinBlood vesselBladderHeart

With printing tissues, by 2012, there were four accepted standard levels of regenerative complexity that were acknowledged in various academic institutions:

  • Level one, flat tissue like skin was the simplest to recreate; [3]
  • Level two was tubular structures such as blood vessels; [3]
  • Level three was hollow non-tubular structures; [3]
  • Level four was solid organs, which were by far the most complex to recreate due to the vascularity. [3]

In 2012, within 60 days it was possible, inside the lab, to grow tissue the size of half a postage stamp to the size of a football field; and most cell types could be grown and expanded outside of the body, with the exception of the liver, nerve and pancreas, as these tissue types need stem cell populations. [3]

Regeneration with drugs

In 2016 scientistc could transform skin into other tissue with molecules. In 2017 scientists could transform many tissue types into skin. Mantoux tuberculin skin test.jpg
In 2016 scientistc could transform skin into other tissue with molecules. In 2017 scientists could transform many tissue types into skin.

Lipoatrophy is the localised loss of fat in tissue. It is common in diabetics who use conventional insulin injection treatment. [4] In 1949 a much more pure form of insulin was, instead of causing lipoatrophy, shown to regenerate the localised loss of fat after injections in to diabetics. [4] In 1984 it was shown that different insulin injections have different regenerative responses with regards to creating skin fats in the same person. [5] It was shown in the same body that conventional forms of insulin injections cause lipoatrophy and highly purified insulin injections cause lipohypertrophy. [5] In 1976 the regenerative response was shown to work in a non-diabetic after a 3 x 3cm lipoatrophic arm scar was treated with pure monocomponent porcine soluble insulin. [5] [4] A syringe injected insulin under the skin equally in the four quadrants of the defect. [4] To layer four units of insulin evenly into the base of the defect, each quadrant of the defect received one unit of insulin three times a day, for eighty-two days. [4] After eighty-two days of consecutive injections the defect regenerated to normal tissue. [4] [5]

In 2016 scientists could transform a skin cell into any other tissue type via the use of drugs. [6] The technique was noted as safer than genetic reprogramming which, in 2016, was a concern medically. [6] The technique, used a cocktail of chemicals and enabled efficient on site regeneration without any genetic programming. [6] In 2016 it was hoped to one day use this drug to regenerate tissue at the site of tissue injury. [6] In 2017, scientists could turn many cell types (such as brain and heart) into skin. [19]

Naturally regenerating appendages and organs


Cardiomyocyte necrosis activates an inflammatory response that serves to clear the injured myocardium from dead cells, and stimulates repair, but may also extend injury. Research suggests that the cell types involved in the process play an important role. Namely monocyte-derived macrophages tend to induce inflammation while inhibiting cardiac regeneration, while tissue resident macrophages may help restoration of tissue structure and function. [20]


The endometrium after the process of breakdown via the menstruation cycle, re-epithelializes swiftly and regenerates. [21] Though tissues with a non-interrupted morphology, like non-injured soft tissue, completely regenerate consistently; the endometrium is the only human tissue that completely regenerates consistently after a disruption and interruption of the morphology. [21]


In May 1932, L.H. McKim published a report in The Canadian Medical Association Journal, that described the regeneration of an adult digit-tip following amputation. A house surgeon in the Montreal General Hospital underwent amputation of the distal phalanx to stop the spread of an infection. In less than one month following surgery, x-ray analysis showed the regrowth of bone while macroscopic observation showed the regrowth of nail and skin. [22] This is one of the earliest recorded examples of adult human digit-tip regeneration. [23]

Studies in the 1970s showed that children up to the age of 10 or so who lose fingertips in accidents can regrow the tip of the digit within a month provided their wounds are not sealed up with flaps of skin the de facto treatment in such emergencies. They normally won't have a fingerprint, and if there is any piece of the finger nail left it will grow back as well, usually in a square shape rather than round. [24] [25]

In August 2005, Lee Spievack, then in his early sixties, accidentally sliced off the tip of his right middle finger just above the first phalanx. His brother, Dr. Alan Spievack, was researching regeneration and provided him with powdered extracellular matrix, developed by Dr. Stephen Badylak of the McGowan Institute of Regenerative Medicine. Mr. Spievack covered the wound with the powder, and the tip of his finger re-grew in four weeks. [26] The news was released in 2007. Ben Goldacre has described this as "the missing finger that never was", claiming that fingertips regrow and quoted Simon Kay, professor of hand surgery at the University of Leeds, who from the picture provided by Goldacre described the case as seemingly "an ordinary fingertip injury with quite unremarkable healing" [27]

A similar story was reported by CNN. A woman named Deepa Kulkarni lost the tip of her little finger and was initially told by doctors that nothing could be done. Her personal research and consultation with several specialists including Badylak eventually resulted in her undergoing regenerative therapy and regaining her fingertip. [28]


Regenerative capacity of the kidney has been recently explored. [29]

The basic functional and structural unit of the kidney is nephron, which is mainly composed of four components: the glomerulus, tubules, the collecting duct and peritubular capillaries. The regenerative capacity of the mammalian kidney is limited compared to that of lower vertebrates.

In the mammalian kidney, the regeneration of the tubular component following an acute injury is well known. Recently regeneration of the glomerulus has also been documented. Following an acute injury, the proximal tubule is damaged more, and the injured epithelial cells slough off the basement membrane of the nephron. The surviving epithelial cells, however, undergo migration, dedifferentiation, proliferation, and redifferentiation to replenish the epithelial lining of the proximal tubule after injury. Recently, the presence and participation of kidney stem cells in the tubular regeneration has been shown. However, the concept of kidney stem cells is currently emerging. In addition to the surviving tubular epithelial cells and kidney stem cells, the bone marrow stem cells have also been shown to participate in regeneration of the proximal tubule, however, the mechanisms remain controversial. Recently, studies examining the capacity of bone marrow stem cells to differentiate into renal cells are emerging. [30]

Like other organs, the kidney is also known to regenerate completely in lower vertebrates such as fish. Some of the known fish that show remarkable capacity of kidney regeneration are goldfish, skates, rays, and sharks. In these fish, the entire nephron regenerates following injury or partial removal of the kidney.


The human liver is particularly known for its ability to regenerate, and is capable of doing so from only one quarter of its tissue, [31] due chiefly to the unipotency of hepatocytes. [32] Resection of liver can induce the proliferation of the remaining hepatocytes until the lost mass is restored, where the intensity of the liver's response is directly proportional to the mass resected. For almost 80 years surgical resection of the liver in rodents has been a very useful model to the study of cell proliferation. [33] [34]


Toes damaged by gangrene and burns in older people can also regrow with the nail and toe print returning after medical treatment for gangrene. [35]

Vas deferens

The vas deferens can grow back together after a vasectomy thus resulting in vasectomy failure. [36] This occurs due to the fact that the epithelium of the vas deferens, similar to the epithelium of some other human body parts, is capable of regenerating and creating a new tube in the event that the vas deferens is damaged and/or severed. [37] Even when as much as five centimeters, or two inches, of the vas deferens is removed, the vas deferens can still grow back together and become reattachedthus allowing sperm to once again pass and flow through the vas deferens, restoring one's fertility. [37]

Induced regeneration in humans

There are now several human tissues that have been successfully or partially induced to regenerate. Many of these examples fall under the topic of regenerative medicine, which includes the methods and research conducted with the aim of regenerating the organs and tissues of humans as a result of injury. The major strategies of regenerative medicine include dedifferentiating injury site cells, transplanting stem cells, implanting lab-grown tissues and organs, and implanting bioartificial tissues.


In 1999 the bladder was the first regenerated organ to be given to seven patients; as of 2014, these regenerated bladders are still functioning inside the beneficiaries. [14]


In 1949 purified insulin was shown to regenerate fat in diabetics with lipoatrophy. [4] In 1976,after 82 days of consecutive injections into a scar, purified insulin was shown to safely regenerate fat and completely regenerate skin in a non-diabetic. [4] [5]

During a high-fat diet, and during hair follicle growth, mature adipocytes (fats) are naturally formed in multiple tissues. [38] Fat tissue has been implicated in the inducement of tissue regeneration. Myofibroblasts are the fibroblast responsible for scar and in 2017 it was found that the regeneration of fat transformed myofibroblasts into adipocytes instead of scar tissue. [39] [38] Scientists also identified bone morphogenetic protein (BMP) signalling as important for myofibroblasts transforming into adipocytes for the purpose of skin and fat regeneration. [39]


Cardiovascular diseases are the leading cause of death worldwide, and have increased proportionally from 25.8% of global deaths in 1990, to 31.5% of deaths in 2013. [40] This is true in all areas of the world except Africa. [40] [41] In addition, during a typical myocardial infarction or heart attack, an estimated one billion cardiac cells are lost. [42] The scarring that results is then responsible for greatly increasing the risk of life-threatening abnormal heart rhythms or arrhythmias. Therefore, the ability to naturally regenerate the heart would have an enormous impact on modern healthcare. However, while several animals can regenerate heart damage (e.g. the axolotl), mammalian cardiomyocytes (heart muscle cells) cannot proliferate (multiply) and heart damage causes scarring and fibrosis.

Despite the earlier belief that human cardiomyocytes are not generated later in life, a recent study has found that this is not the case. This study took advantage of the nuclear bomb testing during the Cold War, which introduced carbon-14 into the atmosphere and therefore into the cells of nearby inhabitants. [43] They extracted DNA from the myocardium of these research subjects and found that cardiomyocytes do in fact renew at a slowing rate of 1% per year from the age of 25, to 0.45% per year at the age of 75. [43] This amounts to less than half of the original cardiomyocytes being replaced during the average lifespan. However, serious doubts have been placed on the validity of this research, including the appropriateness of the samples as representative of normally aging hearts. [44]

Regardless, further research has been conducted that supports the potential for human cardiac regeneration. Inhibition of p38 MAP kinase was found to induce mitosis in adult mammalian cardiomyocytes, [45] while treatment with FGF1 and p38 MAP kinase inhibitors was found to regenerate the heart, reduce scarring, and improve cardiac function in rats with cardiac injury. [46]

One of the most promising sources of heart regeneration is the use of stem cells. It was demonstrated in mice that there is a resident population of stem cells or cardiac progenitors in the adult heart – this population of stem cells was shown to be reprogrammed to differentiate into cardiomyocytes that replaced those lost during a heart tissue death. [47] In humans specifically, a “cardiac mesenchymal feeder layer” was found in the myocardium that renewed the cells with progenitors that differentiated into mature cardiac cells. [48] What these studies show is that the human heart contains stem cells that could potentially be induced into regenerating the heart when needed, rather than just being used to replace expended cells.

Loss of the myocardium due to disease often leads to heart failure; therefore, it would be useful to be able to take cells from elsewhere in the heart to replenish those lost. This was achieved in 2010 when mature cardiac fibroblasts were reprogrammed directly into cardiomyocyte-like cells. This was done using three transcription factors: GATA4, Mef2c, and Tbx5. [49] Cardiac fibroblasts make up more than half of all heart cells and are usually not able to conduct contractions (are not cardiogenic), but those reprogrammed were able to contract spontaneously. [49] The significance is that fibroblasts from the damaged heart or from elsewhere, may be a source of functional cardiomyocytes for regeneration.

Simply injecting functioning cardiac cells into a damaged heart is only partially effective. In order to achieve more reliable results, structures composed of the cells need to be produced and then transplanted. Masumoto and his team designed a method of producing sheets of cardiomyocytes and vascular cells from human iPSCs. These sheets were then transplanted onto infarcted hearts of rats, leading to significantly improved cardiac function. [50] These sheets were still found to be present four weeks later. [50] Research has also been conducted into the engineering of heart valves. Tissue-engineered heart valves derived from human cells have been created in vitro and transplanted into a non-human primate model. These showed a promising amount of cellular repopulation even after eight weeks, and succeeded in outperforming currently-used non-biological valves. [51] In April 2019, researchers 3d printed a prototype human heart to the size of a rabbits heart. [18]


Chronic obstructive pulmonary disease (COPD) is one of the most widespread health threats today. It affects 329 million people worldwide, which makes up nearly 5% of the global population. Having killed over 3 million people in 2012, COPD was the third greatest cause of death. [52] Worse still is that due to increasing smoking rates and the aging populations in many countries, the number of deaths as a result of COPD and other chronic lung diseases is predicted to continue increasing. [53] Therefore, developments in the lung's capacity for regeneration is in high demand.

It has been shown that bone marrow-derived cells could be the source of progenitor cells of multiple cell lineages, and a 2004 study suggested that one of these cell types was involved in lung regeneration. [54] Therefore, a potential source of cells for lung regeneration has been found; however, due to advances in inducing stem cells and directing their differentiation, major progress in lung regeneration has consistently featured the use of patient-derived iPSCs and bioscaffolds. The extracellular matrix is the key to generating entire organs in vitro. It was found that by carefully removing the cells of an entire lung, a "footprint" is left behind that can guide cellular adhesion and differentiation if a population of lung epithelial cells and chondrocytes are added. [55] This has serious applications in regenerative medicine, particularly as a 2012 study successfully purified a population of lung progenitor cells that were derived from embryonic stem cells. These can then be used to re-cellularise a three-dimensional lung tissue scaffold. [56]

Indeed, in 2008, there was a successful clinical transplantation of a tissue-engineered trachea in a 30-year-old woman with end-stage bronchomalacia. An ECM scaffold was created by removing the cells and MHC antigens from a human donated trachea, which was then colonised by epithelial cells and mesenchymal stem cell-derived chondrocytes cultured from cells of the recipient. [57] The graft replaced her left main bronchus, immediately providing a functional airway, and retained its normal appearance and mechanical function after four months. [57] Because the graft was generated from cells cultured from the recipient, no anti-donor antibodies or immunosuppressive drugs were needed—a huge step towards personalised lung regeneration.

A 2010 investigation took this one step further by using the ECM scaffold to produce entire lungs in vitro to be transplanted into living rats. [58] These successfully enabled gas exchange but for short time intervals only. [58] Nevertheless, this was a huge leap towards whole lung regeneration and transplants for humans, which has already taken another step forward with the lung regeneration of a non-human primate. [59]

Cystic fibrosis is another disease of the lungs, which is highly fatal and genetically linked to a mutation in the CFTR gene. Through growing patient-specific lung epithelium in vitro, lung tissue expressing the cystic fibrosis phenotype has been achieved. [60] This is so that modelling and drug testing of the disease pathology can be carried out with the hope of regenerative medical applications.


The penis has been successfully regenerated in the lab. [14] The penis is a harder organ to regenerate than skin, the bladder, and the vagina due to its structural complexity. [14]

Spinal nerves

A goal of spinal cord injury research is to promote neuroregeneration, reconnection of damaged neural circuits. [61] The nerves in the spine are a tissue that requires a stem cell population to regenerate. In 2012 a Polish fireman Darek Fidyka, with paraplegia of the spinal cord, underwent a procedure, which involved extracting olfactory ensheathing cells (OECs) from Fidyka's olfactory bulbs, and injecting these stem cells, in vivo, into the site of the previous injury. Fidyka eventually gained feeling, movement and sensation in his limbs, especially on the side where the stem cells were injected; he also reported gaining sexual function. Fidyka can now drive and can now walk some distance aided by a frame. He is believed to be the first person in the world to recover sensory function from a complete severing of the spinal nerves. [62] [63]


Researchers from the University of Edinburgh have succeeded in regenerating a living organ. The regenerated organ closely resembled a juvenile thymus in terms of architecture and gene expression profile. [64] The thymus gland is one of the first organs to degenerate in normal healthy individuals.


Between the years 2005 and 2008, four women with vaginal hypoplasia due to Müllerian agenesis were given regenerated vaginas. [65] Up to eight years after the transplants, all organs have normal function and structure. [14]

See also

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An artificial organ is a human made organ device or tissue that is implanted or integrated into a human — interfacing with living tissue — to replace a natural organ, to duplicate or augment a specific function or functions so the patient may return to a normal life as soon as possible. The replaced function does not have to be related to life support, but it often is. For example, replacement bones and joints, such as those found in hip replacements, could also be considered artificial organs.

Tissue engineering Biomedical engineering discipline

Tissue engineering is a biomedical engineering discipline that uses a combination of cells, engineering, materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biological tissues. Tissue engineering often involves the use of cells placed on tissue scaffolds in the formation of new viable tissue for a medical purpose but is not limited to applications involving cells and tissue scaffolds. While it was once categorized as a sub-field of biomaterials, having grown in scope and importance it can be considered as a field in its own.

Regeneration (biology) Biological process of renewal, restoration, and tissue growth

In biology, regeneration 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. Every species is capable of regeneration, from bacteria to humans. Regeneration can either be complete where the new tissue is the same as the lost tissue, or incomplete where after the necrotic tissue comes fibrosis.

Fibrosis Formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process

Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of permanent scar tissue.

Regenerative medicine Field of medicine involved in regenerating tissues

Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by stimulating the body's own repair mechanisms to functionally heal previously irreparable tissues or organs.

Cell therapy Therapy in which cellular material is injected into a patient

Cell therapy is a therapy in which viable cells are injected, grafted or implanted into a patient in order to effectuate a medicinal effect, for example, by transplanting T-cells capable of fighting cancer cells via cell-mediated immunity in the course of immunotherapy, or grafting stem cells to regenerate diseased tissues.

Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition. As of 2016, the only established therapy using stem cells is hematopoietic stem cell transplantation. This usually takes the form of a bone-marrow transplantation, but the cells can also be derived from umbilical cord blood. Research is underway to develop various sources for stem cells as well as to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes and heart disease.

Transplantable organs and tissues may both refer to organs and tissues that are relatively often or routinely transplanted, as well as relatively seldom transplanted organs and tissues and ones on the experimental stage.

Cellular cardiomyoplasty, or cell-based cardiac repair, is a new potential therapeutic modality in which progenitor cells are used to repair regions of damaged or necrotic myocardium. The ability of transplanted progenitor cells to improve function within the failing heart has been shown in experimental animal models and in some human clinical trials. In November 2011, a large group of collaborators at Minneapolis Heart Institute Foundation at Abbott Northwestern found no significant difference in left ventricular ejection fraction (LVEF) or other markers, between a group of patients treated with cellular cardiomyoplasty and a group of control patients. In this study, all patients were post MI, post percutaneous coronary intervention (PCI) and that infusion of progenitor cells occurred 2–3 weeks after intervention. In a study that is currently underway, however, more positive results were being reported: In the SCIPIO trial, patients treated with autologous cardiac stem cells post MI have been reported to be showing statistically significant increases in LVEF and reduction in infarct size over the control group at four months after implant. Positive results at the one-year mark are even more pronounced. Yet the SCIPIO trial "was recently called into question". Harvard University is "now investigating the integrity of some of the data". The Lancet recently published a non-specific ‘Expression of concern’ about the paper. Subsequently, another preclinical study also raised doubts on the rationale behind using this special kind of cell, as it was found that the special cells only have a minimal ability in generating new cardiomyocytes. Some specialists therefore now raise concerns to continue.

Dermal fibroblasts are cells within the dermis layer of skin which are responsible for generating connective tissue and allowing the skin to recover from injury. Using organelles, dermal fibroblasts generate and maintain the connective tissue which unites separate cell layers. Furthermore, these dermal fibroblasts produce the protein molecules including laminin and fibronectin which comprise the extracellular matrix. By creating the extracellular matrix between the dermis and epidermis, fibroblasts allow the epithelial cells of the epidermis to affix the matrix, thereby allowing the epidermal cells to effectively join together to form the top layer of the skin.


Decellularization is the process used in biomedical engineering to isolate the extracellular matrix (ECM) of a tissue from its inhabiting cells, leaving an ECM scaffold of the original tissue, which can be used in artificial organ and tissue regeneration. Organ and tissue transplantation treat a variety of medical problems, ranging from end organ failure to cosmetic surgery. One of the greatest limitations to organ transplantation derives from organ rejection caused by antibodies of the transplant recipient reacting to donor antigens on cell surfaces within the donor organ. Because of unfavorable immune responses, transplant patients suffer a lifetime taking immunosuppressing medication. Stephen F. Badylak pioneered the process of decellularization at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. This process creates a natural biomaterial to act as a scaffold for cell growth, differentiation and tissue development. By recellularizing an ECM scaffold with a patient’s own cells, the adverse immune response is eliminated. Nowadays, commercially available ECM scaffolds are available for a wide variety of tissue engineering. Using peracetic acid to decellularize ECM scaffolds have been found to be false and only disinfects the tissue.

Endogenous cardiac stem cells (eCSCs) are tissue-specific stem progenitor cells harboured within the adult mammalian heart. It has to be noted that a scientific-misconduct scandal, involving Harvard professor Piero Anversa, might indicate that the heart stem cell concept be broken. Therefore, the following article should be read with caution, as it builds on Anversa's results.

Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor or unipotent – (iUSC) according to their developmental potential and degree of dedifferentiation. Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells.

A Muse cell is an endogenous non-cancerous pluripotent stem cell. They reside in the connective tissue of nearly every organ including the umbilical cord, bone marrow and peripheral blood. They are collectable from commercially obtainable mesenchymal cells such as human fibroblasts, bone marrow-mesenchymal stem cells and adipose-derived stem cells. Muse cells are able to generate cells representative of all three germ layers from a single cell both spontaneously and under cytokine induction. Expression of pluripotency genes and triploblastic differentiation are self-renewable over generations. Muse cells do not undergo teratoma formation when transplanted into a host environment in vivo. This can be explained in part by their intrinsically low telomerase activity, eradicating the risk of tumorigenesis through unbridled cell proliferation. They were discovered in 2010 by Mari Dezawa and her research group. Clinical trials for acute myocardial infarction, stroke, epidermolysis bullosa, spinal cord injury, amyotrophic lateral sclerosis, acute respiratory distress syndrome (ARDS) related to novel coronavirus (SARS-CoV-2) infection, are conducted by Life Science Institute, Inc., a group company of Mitsubishi Chemical Holdings company. Physician-led clinical trial for neonatal hypoxic-ischemic encephalopathy was also started. The summary results of a randomized double-blind placebo-controlled clinical trial in patients with stroke was announced.

Human engineered cardiac tissues (hECTs) are derived by experimental manipulation of pluripotent stem cells, such as human embryonic stem cells (hESCs) and, more recently, human induced pluripotent stem cells (hiPSCs) to differentiate into human cardiomyocytes. Interest in these bioengineered cardiac tissues has risen due to their potential use in cardiovascular research and clinical therapies. These tissues provide a unique in vitro model to study cardiac physiology with a species-specific advantage over cultured animal cells in experimental studies. hECTs also have therapeutic potential for in vivo regeneration of heart muscle. hECTs provide a valuable resource to reproduce the normal development of human heart tissue, understand the development of human cardiovascular disease (CVD), and may lead to engineered tissue-based therapies for CVD patients.

A bioartificial heart is an engineered heart that contains the extracellular structure of a decellularized heart and cellular components from a different source. Such hearts are of particular interest for therapy as well as research into heart disease. The first bioartificial hearts were created in 2008 using cadaveric rat hearts. In 2014, human-sized bioartificial pig hearts were constructed. Bioartificial hearts have not been developed yet for clinical use, although the recellularization of porcine hearts with human cells opens the door to xenotransplantation.

Cellular Dynamics International

Fujifilm Cellular Dynamics, Inc. (FCDI) is a large scale manufacturer of human cells, created from induced pluripotent stem cells, for use in basic research, drug discovery and regenerative medicine applications.

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. Scar improvement, and scar-free healing are an important and relevant area of medicine. During the 1990s, published research on the subject increased; it's a relatively recent term in the literature. Scar free healing is something which takes place in foetal life but the capacity is lost during progression to adulthood. In amphibians, tissue regeneration occurs, for example, as in skin regeneration in the adult axolotl.

Ischemia-reperfusion (IR) tissue injury is the resultant pathology from a combination of factors, including tissue hypoxia, followed by tissue damage associated with re-oxygenation. IR injury contributes to disease and mortality in a variety of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Whether resulting from traumatic vessel disruption, tourniquet application, or shock, the extremity is exposed to an enormous flux in vascular perfusion during a critical period of tissue repair and regeneration. The contribution of this ischemia and subsequent reperfusion on post-traumatic musculoskeletal tissues is unknown; however, it is likely that similar to cardiac and kidney tissue, IR significantly contributes to tissue fibrosis.

Cardiomyocyte proliferation refers to the ability of cardiac muscle cells to progress through the cell cycle and continue to divide. Traditionally, cardiomyocytes were believed to have little to no ability to proliferate and regenerate after birth. Although other types of cells, such as gastrointestinal epithelial cells, can proliferate and differentiate throughout life, cardiac tissue contains little intrinsic ability to proliferate, as adult human cells arrest in the cell cycle. However, a recent paradigm shift has occurred. Recent research has demonstrated that human cardiomyocytes do proliferate to a small extent for the first two decades of life. Also, cardiomyocyte proliferation and regeneration has been demonstrated to occur in various neonatal mammals in response to injury in the first week of life. Current research aims to further understand the biological mechanism underlying cardiomyocyte proliferation in hopes to turn this capability back on in adults in order to combat heart disease.


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