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In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell in a cell lineage. They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells, which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type.
Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology caused by teratogens. Teratogens are substances that may cause non-heritable birth defects via a toxic effect on an embryo or fetus. Defects include malformations, disruptions, deformations, and dysplasia that may cause stunted growth, delayed mental development, or other congenital disorders that lack structural malformations. The related term developmental toxicity includes all manifestations of abnormal development that are caused by environmental insult. The extent to which teratogens will impact an embryo is dependent on several factors, such as how long the embryo has been exposed, the stage of development the embryo was in when exposed, the genetic makeup of the embryo, and the transfer rate of the teratogen.
Anencephaly is the absence of a major portion of the brain, skull, and scalp that occurs during embryonic development. It is a cephalic disorder that results from a neural tube defect that occurs when the rostral (head) end of the neural tube fails to close, usually between the 23rd and 26th day following conception. Strictly speaking, the Greek term translates as "without a brain", but it is accepted that children born with this disorder usually only lack a telencephalon, the largest part of the brain consisting mainly of the cerebral hemispheres, including the neocortex, which is responsible for cognition. The remaining structure is usually covered only by a thin layer of membrane—skin, bone, meninges, etc., are all lacking. With very few exceptions, infants with this disorder do not survive longer than a few hours or days after birth.
A birth defect is an abnormal condition that is present at birth, regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth defects are divided into two main types: structural disorders in which problems are seen with the shape of a body part and functional disorders in which problems exist with how a body part works. Functional disorders include metabolic and degenerative disorders. Some birth defects include both structural and functional disorders.
Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin. Choline also prevents fat deposits in the liver and facilitates the movement of fats into cells.
Adult neurogenesis is the process in which neurons are generated from neural stem cells in the adult. This process differs from prenatal neurogenesis.
Neural engineering is a discipline within biomedical engineering that uses engineering techniques to understand, repair, replace, or enhance neural systems. Neural engineers are uniquely qualified to solve design problems at the interface of living neural tissue and non-living constructs.
Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells, they can be found in juvenile, adult animals, and humans, unlike embryonic stem cells.
Neural tube defects (NTDs) are a group of birth defects in which an opening in the spine or cranium remains from early in human development. In the third week of pregnancy called gastrulation, specialized cells on the dorsal side of the embryo begin to change shape and form the neural tube. When the neural tube does not close completely, an NTD develops.
Stem-cell therapy uses stem cells to treat or prevent a disease or condition. As of 2024, the only FDA-approved therapy using stem cells is hematopoietic stem cell transplantation. This usually takes the form of a bone marrow or peripheral blood stem cell 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.
Neural stem cells (NSCs) are self-renewing, multipotent cells that firstly generate the radial glial progenitor cells that generate the neurons and glia of the nervous system of all animals during embryonic development. Some neural progenitor stem cells persist in highly restricted regions in the adult vertebrate brain and continue to produce neurons throughout life. Differences in the size of the central nervous system are among the most important distinctions between the species and thus mutations in the genes that regulate the size of the neural stem cell compartment are among the most important drivers of vertebrate evolution.
An amniotic epithelial cell is a form of stem cell extracted from the lining of the inner membrane of the placenta. Amniotic epithelial cells start to develop around 8 days post fertilization. These cells are known to have some of the same markers as embryonic stem cells, more specifically, Oct-4 and nanog. These transcription factors are the basis of the pluripotency of stem cells. Amniotic epithelial cells have the ability to develop into any of the three germ layers: endoderm, mesoderm, and ectoderm. They can develop into several organ tissues specific to these germ layers including heart, brain, and liver. The pluripotency of the human amniotic epithelial cells makes them useful in treating and fighting diseases and disorders of the nervous system as well as other tissues of the human body. Artificial heart valves and working tracheas, as well as muscle, fat, bone, heart, neural and liver cells have all been engineered using amniotic stem cells. Tissues obtained from amniotic cell lines show promise for patients with congenital diseases or malformations of the heart, liver, lungs, kidneys, and cerebral tissue.
Nervous system diseases, also known as nervous system or neurological disorders, refers to a small class of medical conditions affecting the nervous system. This category encompasses over 600 different conditions, including genetic disorders, infections, cancer, seizure disorders, conditions with a cardiovascular origin, congenital and developmental disorders, and degenerative disorders.
Fibrochondrogenesis is a rare autosomal recessive form of osteochondrodysplasia, causing abnormal fibrous development of cartilage and related tissues.
A neural, or brain organoid, describes an artificially grown, in vitro, tissue resembling parts of the human brain. Neural organoids are created by culturing pluripotent stem cells into a three-dimensional culture that can be maintained for years. The brain is an extremely complex system of heterogeneous tissues and consists of a diverse array of neurons and glial cells. This complexity has made studying the brain and understanding how it works a difficult task in neuroscience, especially when it comes to neurodevelopmental and neurodegenerative diseases. The purpose of creating an in vitro neurological model is to study these diseases in a more defined setting. This 3D model is free of many potential in vivo limitations. The varying physiology between human and other mammalian models limits the scope of animal studies in neurological disorders. Neural organoids contain several types of nerve cells and have anatomical features that recapitulate regions of the nervous system. Some neural organoids are most similar to neurons of the cortex. In some cases, the retina, spinal cord, thalamus and hippocampus. Other neural organoids are unguided and contain a diversity of neural and non-neural cells. Stem cells have the potential to grow into many different types of tissues, and their fate is dependent on many factors. Below is an image showing some of the chemical factors that can lead stem cells to differentiate into various neural tissues; a more in-depth table of generating specific organoid identity has been published. Similar techniques are used on stem cells used to grow cerebral organoids.
A cholinergic neuron is a nerve cell which mainly uses the neurotransmitter acetylcholine (ACh) to send its messages. Many neurological systems are cholinergic. Cholinergic neurons provide the primary source of acetylcholine to the cerebral cortex, and promote cortical activation during both wakefulness and rapid eye movement sleep. The cholinergic system of neurons has been a main focus of research in aging and neural degradation, specifically as it relates to Alzheimer's disease. The dysfunction and loss of basal forebrain cholinergic neurons and their cortical projections are among the earliest pathological events in Alzheimer's disease.
Sergiu P. Pașca is a Romanian-American scientist and physician at Stanford University in California. He is renowned for his groundbreaking work creating and developing stem cell-based models of the human brain to gain insights into neuropsychiatric disease. His lab was the first to develop and name assembloids: multi-unit self-organizing structures created in 3D cultures that allow for the study of human neural circuit and systems functions in vitro. Pașca’s lab generated and published human cortico-striatal and cortico-motor assembloids in 2020. Combining regionalized neural organoids pioneered in the lab and studies with human forebrain assembloids and transplantation, in 2024, Pașca developed a therapeutic for a severe genetic disorder called Timothy Syndrome, which was published on the cover of Nature.
Cell-based therapies for Parkinson's disease include various investigational procedures which transplant specific populations of cells into the brains of people with Parkinson's disease. The investigation of cell transplantation therapies followed the discovery that the death of dopaminergic neurons in the substantia nigra pars compacta resulted in the motor symptoms of the disease. Thus, cell transplantation has focused on various dopamine producing cells throughout the body.
Shiverer mice are mice which possess the shiverer (shi/shi) mutation in the MBP gene. Shiverer mice develop a characteristic "shaking" or "shivering" gait within a few weeks of birth. They are commonly used as animal models of leukodystrophy in neuroscience research.
Phenserine is a synthetic drug which has been investigated as a medication to treat Alzheimer's disease (AD), as the drug exhibits neuroprotective and neurotrophic effects.
References
- ↑ Yanai, Joseph; Vigoda, Myles J.; Ornoy, Asher (August 2019). "Reversal of neurobehavioral teratogenicity in animal models and human: Three decades of progress". Brain Research Bulletin. 150: 328–342. doi:10.1016/j.brainresbull.2019.06.009. ISSN 0361-9230. PMID 31207281. S2CID 189820103.
- ↑ "Professor Joseph Yanai". The Hebrew University of Jerusalem.
- ↑ "Behavior genetics association abstracts". Behavior Genetics. 3 (4): 393–419. December 1973. doi:10.1007/bf01070223. ISSN 0001-8244. S2CID 189854750.
- ↑ "Behavior genetics association abstracts". Behavior Genetics. 3 (4): 393–419. December 1973. doi:10.1007/bf01070223. ISSN 0001-8244. S2CID 189854750.
- ↑ Yanai, Joseph; Beer, Avital; Huleihel, Rabab; Izrael, Michal; Katz, Sofia; Levi, Yaarit; Rozenboim, Israel; Yaniv, Shiri P.; Slotkin, Theodore A. (October 2004). "Convergent Effects on Cell Signaling Mechanisms Mediate the Actions of Different Neurobehavioral Teratogens: Alterations in Cholinergic Regulation of Protein Kinase C in Chick and Avian Models". Annals of the New York Academy of Sciences. 1025 (1): 595–601. doi:10.1196/annals.1316.074. ISSN 0077-8923. PMID 15542768. S2CID 10927050.
- ↑ Joseph Yanai, ed. (1984). Neurobehavioral teratology. Amsterdam: Elsevier. ISBN 0-444-80516-8. OCLC 10275574.
- ↑ Yanai, Joseph; Laxer, Uri; Pick, Chaim G.; Trombka, David (August 1989). "Dopaminergic denervation reverses behavioral deficits induced by prenatal exposure to phenobarbital". Developmental Brain Research. 48 (2): 255–261. doi:10.1016/0165-3806(89)90080-1. ISSN 0165-3806. PMID 2505945.
- ↑ Beer, Avital; Slotkin, Theodore A; Seidler, Frederic J; Aldridge, Justin E; Yanai, Joseph (2004-10-20). "Nicotine Therapy in Adulthood Reverses the Synaptic and Behavioral Deficits Elicited by Prenatal Exposure to Phenobarbital". Neuropsychopharmacology. 30 (1): 156–165. doi: 10.1038/sj.npp.1300582 . ISSN 0893-133X. PMID 15496940.
- ↑ Yanai, Joseph; Pick, Chaim G. (1988). "Neuron transplantation reverses phenobarbital-induced behavioral birth defects in mice". International Journal of Developmental Neuroscience. 6 (5): 409–416. doi:10.1016/0736-5748(88)90046-9. ISSN 0736-5748. PMID 3202000. S2CID 23370083.
- ↑ Kazma, Meital; Izrael, Michal; Revel, Michel; Chebath, Judith; Yanai, Joseph (2010-02-01). "Survival, differentiation, and reversal of heroin neurobehavioral teratogenicity in mice by transplanted neural stem cells derived from embryonic stem cells". Journal of Neuroscience Research. 88 (2): 315–323. doi:10.1002/jnr.22193. ISSN 0360-4012. PMID 19746435. S2CID 24682086.
- ↑ Turgeman, Gadi; Pinkas, Adi; Slotkin, Theodore A.; Tfilin, Matanel; Langford, Rachel; Yanai, Joseph (2011-04-21). "Reversal of chlorpyrifos neurobehavioral teratogenicity in mice by allographic transplantation of adult subventricular zone-derived neural stem cells". Journal of Neuroscience Research. 89 (8): 1185–1193. doi:10.1002/jnr.22631. ISSN 0360-4012. PMID 21520219. S2CID 3424029.
- ↑ Yanai, Joseph; Vigoda, Myles J.; Ornoy, Asher (August 2019). "Reversal of neurobehavioral teratogenicity in animal models and human: Three decades of progress". Brain Research Bulletin. 150: 328–342. doi:10.1016/j.brainresbull.2019.06.009. ISSN 0361-9230. PMID 31207281. S2CID 189820103.
- ↑ "Stem cell therapy may reverse brain birth defects". Oneindia.com. 30 December 2008.
- ↑ "Health Scan: Stem cell therapy may reverse brain defects". The Jerusalem Post.
- ↑ Ben-Shaanan, T L; Ben-Hur, T; Yanai, J (2007-09-18). "Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain". Molecular Psychiatry. 13 (2): 222–231. doi: 10.1038/sj.mp.4002084 . ISSN 1359-4184. PMID 17876325. S2CID 12784221.
- ↑ Ben-Shaanan, TL, Ben-Hur, T, and Yanai, J.: “Transplantation of neural progenitors enhances production of endogeneous cells in the impaired brain”. Molecular Psychiatry, September 18, 2007. Vol. 13, No. 2, pp222-231
- ↑ "Hebrew University Scientists Succeed Through Stem Cell Therapy in Reversing Brain Birth Defects". Technology Networks.
- ↑ "Stem Cells Undo Birth Defects". MIT Technology Review.
- ↑ Yanai, Joseph (May 2016). "Fortieth Anniversary Annual Meeting of the Developmental Neurotoxicology Society Held in Conjunction with the 56th Annual Meeting of the Teratology Society Grand Hyatt San Antonio, San Antonio, Texas June 25–29, 2016". Neurotoxicology and Teratology. 55: 58–75. doi:10.1016/j.ntt.2016.04.003. ISSN 0892-0362.
- ↑ Yanai, Joseph; Vigoda, Myles J.; Ornoy, Asher (August 2019). "Reversal of neurobehavioral teratogenicity in animal models and human: Three decades of progress". Brain Research Bulletin. 150: 328–342. doi:10.1016/j.brainresbull.2019.06.009. ISSN 0361-9230. PMID 31207281. S2CID 189820103.