Adult stem cell
Adult stem cell | |
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electron micrograph of an adult stem cell displaying typical ultrastructural characteristics. | |
Details | |
Identifiers | |
Latin | cellula praecursoria |
MeSH | D053687 |
TH | H1.00.01.0.00035 |
Anatomical terms of microanatomy] |
Adult stem cells are
Scientific interest in adult stem cells is centered around two main characteristics. The first of which is their ability to divide or self-renew indefinitely, and the second their ability to generate all the
Structure
Defining properties
A stem cell possesses two properties:
- Self-renewal is the ability to go through numerous cycles of cell division while still maintaining its undifferentiated state. Stem cells can replicate several times and can result in the formation of two stem cells, one stem cell more differentiated than the other, or two differentiated cells.[3]
- subpopulationof cells possesses stem cell properties in vivo is challenging, and so considerable debate exists as to whether some proposed stem cell populations in the adult are indeed stem cells.
Properties
Cell division
To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter stem cells, whereas asymmetric division produces one stem cell and one
Under normal conditions, tissue stem cells divide slowly and infrequently. They exhibit signs of quiescence or reversible growth arrest.[6] The niche the stem cell is found in plays a large role in maintaining quiescence.[6] Perturbed niches cause the stem cell to begin actively dividing again to replace lost or damaged cells until the niche is restored. In hematopoietic stem cells, the MAPK/ERK pathway and PI3K/AKT/mTOR pathway regulate this transition.[7] The ability to regulate the cell cycle in response to external cues helps prevent stem cell exhaustion or the gradual loss of stem cells following an altered balance between dormant and active states. Infrequent cell divisions also help reduce the risk of acquiring DNA mutations that would be passed on to daughter cells.
Plasticity
Discoveries in recent years have suggested that adult stem cells might have the ability to differentiate into cell types from different germ layers. For instance, neural stem cells from the brain, which are derived from ectoderm, can differentiate into ectoderm, mesoderm, and endoderm.[8] Stem cells from the bone marrow, which is derived from mesoderm, can differentiate into liver, lung, GI tract, and skin, which are derived from endoderm and mesoderm.[9] This phenomenon is referred to as stem cell transdifferentiation or plasticity. It can be induced by modifying the growth medium when stem cells are cultured in vitro or by transplanting them to an organ of the body different from the one they were originally isolated from. There is yet no consensus among biologists on the prevalence and physiological and therapeutic relevance of stem cell plasticity. More recent findings suggest that pluripotent stem cells may reside in blood and adult tissues in a dormant state.[10] These cells are referred to as "Blastomere Like Stem Cells" (BLSCs)[11] and "very small embryonic-like" (VSEL) stem cells, and display pluripotency in vitro.[10] As BLSCs and VSEL cells are present in virtually all adult tissues, including the lungs, brain, kidneys, muscles, and pancreas,[12] co-purification of BLSCs and VSEL cells with other populations of adult stem cells may explain the apparent pluripotency of adult stem cell populations. However, recent studies have shown that both human and murine VSEL cells lack stem cell characteristics and are not pluripotent.[13][14][15][16]
Aging
Stem cell function becomes impaired with age, and this contributes to progressive deterioration of tissue maintenance and repair.[17] A likely important cause of increasing stem cell dysfunction is an age-dependent accumulation of DNA damage in both stem cells and the cells that comprise the stem cell environment.[17] (See also DNA damage theory of aging.)
Adult stem cells can, however, be artificially reverted to a state where they behave like embryonic stem cells (including the associated DNA repair mechanisms). This was done with mice as early as 2006[18] with prospects to slow down human aging substantially.[19] Such cells are one of the various classes of induced stem cells.
Function
Signaling pathways
Adult stem cell research has been focused on uncovering the general molecular mechanisms that control their self-renewal and differentiation.
- Notch
- The mammary[20]stem cells.
- These developmental pathways are also strongly implicated as stem cell regulators.[21]
- The TGFβ family of cytokines regulate the stemness of both normal and cancer stem cells.[22]
Types
Hematopoietic stem cells
Hematopoietic stem cells (HSCs) are stem cells that can differentiate into all blood cells.
Mammary stem cells
Mammary stem cells provide the source of cells for the growth of the mammary gland during puberty and gestation and play an important role in the carcinogenesis of the breast.[27] Mammary stem cells have been isolated from human and mouse tissue as well as from cell lines derived from the mammary gland. Single such cells can give rise to both the luminal and myoepithelial cell types of the gland and have been shown to have the ability to regenerate the entire organ in mice.[27]
Intestinal stem cells
Intestinal stem cells divide continuously throughout life and use a complex
Mesenchymal stem cells
Mesenchymal stem cells (MSCs) are of
Endothelial stem cells
Endothelial stem cells are one of the three types of multipotent stem cells found in the bone marrow. They are a rare and controversial group with the ability to differentiate into endothelial cells, the cells that line blood vessels as well as lymphatic vessels. Endothelial stem cells are an important aspect of the vascular network, even influencing the motion relating to white blood cells.
Neural stem cells
The existence of stem cells in the adult brain has been postulated following the discovery that the process of neurogenesis, the birth of new neurons, continues into adulthood in rats.[35] The presence of stem cells in the mature primate brain was first reported in 1967.[36] It has since been shown that new neurons are generated in adult mice, songbirds, and primates, including humans. Normally, adult neurogenesis is restricted to two areas of the brain – the subventricular zone, which lines the lateral ventricles, and the dentate gyrus of the hippocampal formation.[37] Although the generation of new neurons in the hippocampus is well established, the presence of true self-renewing stem cells there has been debated.[38] Under certain circumstances, such as following tissue damage in ischemia, neurogenesis can be induced in other brain regions, including the neocortex.
Neural stem cells are commonly cultured in vitro as so-called
Neural stem cells share many properties with
Olfactory adult stem cells
Olfactory adult stem cells have been successfully harvested from the human olfactory mucosa cells, which are found in the lining of the nose and are involved in the sense of smell.[43] If they are given the right chemical environment, these cells have the same ability as embryonic stem cells to develop into many different cell types. Olfactory stem cells hold the potential for therapeutic applications and, in contrast to neural stem cells, can be harvested with ease without harm to the patient. This means they can be easily obtained from all individuals, including older patients who might be most in need of stem cell therapies.
Neural crest stem cells
Hair follicles contain two types of stem cells, one of which appears to represent a remnant of the stem cells of the embryonic neural crest. Similar cells have been found in the gastrointestinal tract, sciatic nerve, cardiac outflow tract and spinal and sympathetic ganglia. These cells can generate neurons, Schwann cells, myofibroblasts, chondrocytes, and melanocytes.[44][45]
Testicular cells
Multipotent stem cells with a claimed equivalency to embryonic stem cells have been derived from spermatogonial progenitor cells found in the
Multipotent stem cells have also been derived from germ cells found in human testicles.[55]
Clinical significance
Adult stem cell treatments have been used for many years to successfully treat
Early regenerative applications of adult stem cells have focused on intravenous delivery of blood progenitors known as Hematopoietic Stem Cells (HSCs). CD34+
Therapies
The therapeutic potential of adult stem cells is the focus of much scientific research, due to their ability to be harvested from the parent body that is females during the delivery.[67][68][69] In common with embryonic stem cells, adult stem cells can differentiate into more than one cell type, but unlike the former they are often restricted to certain types or "lineages". The ability of a differentiated stem cell of one lineage to produce cells of a different lineage is called transdifferentiation. Some types of adult stem cells are more capable of transdifferentiation than others, but for many there is no evidence that such a transformation is possible. Consequently, adult stem therapies require a stem cell source of the specific lineage needed, and harvesting and/or culturing them up to the numbers required is a challenge.[70][71] Additionally, cues from the immediate environment (including how stiff or porous the surrounding structure/extracellular matrix is) can alter or enhance the fate and differentiation of the stem cells.[72]
Sources
Research
Cancer
In recent years, acceptance of the concept of adult stem cells has increased. There is now a hypothesis that stem cells reside in many adult tissues and that these unique reservoirs of cells not only are responsible for the normal reparative and regenerative processes but are also considered to be a prime target for genetic and
Multidrug resistance
Adult stem cells express
Lung Organoid Model: Lung Disease in COVID-19
The virus that causes COVID-19, SARS-CoV-2, damages the lungs extensively in the presence of an overreactive immune response. Adult stem cells were extracted from deep lung biopsies and used to construct a complete lung model with both proximal and distal airway epithelia. After being developed in 3D cultures, the organoids were separated into individual cells to form 2D monolayers. These lung models were used to study the damage SARS-CoV-2 causes when applied to the apical side of the transwell.[85]
Stroke Treatment
Due to their
See also
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External links
- NIH Stem Cell Information Resource, a resource for stem cell research
- Nature Reports Stem Cells Background information, research advances, and debates about stem cell science
- UMDNJ Stem Cell and Regenerative Medicine provides educational materials and research resources
- Stem Cell Research at Johns Hopkins University