The SAGE Encyclopedia of Stem Cell Research. Группа авторов
these findings, most scientists remained convinced for a long time that the adult human brain was unable to produce new nerve cells. In the 1990s, however, researchers reached the conclusion that the matured brain did contain stem cells, capable of generating star-shaped glial cells called astrocytes, located in the spinal cord and the brain, and oligodendrocytes, which provide insulation and support to axons, long nerve fiber extensions present in the central nervous system (CNS) of some vertebrates.
While hematopoietic stem cells only produce white blood cells, red blood cells, and platelets, adult stem cells, in contrast, mutate into different kinds of cells susceptible of dividing and reproducing indefinitely.
What are adult stem cells (ASCs) all about? And more specifically, how do they differ from pluripotent stem cells, or rapidly dividing progenitor transit amplifying cells (TACs)? Why are they so important to science and regenerative medicine? What are the challenges, if any, associated to their use?
By definition, “adult stem cells are undifferentiated cells, found throughout the body after embryonic development, that multiply by cell division to replenish dying cells and regenerate damaged tissue.” They are also known as somatic stem cells, found in young and adult animals, and humans.
Many different types of stem cells arise at different locations in the human body, from adult or tissue-specific stem cells, to embryonic stem cells that exist only briefly in the early stages of tissue development. In addition to these, researchers have recently created induced pluripotent stem cells, or iPSCs. These are undifferentiated cells engineered from specialized cells, with characteristics almost identical to those of embryonic stem cells.
Adult or tissue-specific stem cells are deemed to be multipotent, that is, capable of giving rise to a few mature cell types.
Adult stem cells are present in many different tissues and organs, including brain, blood, vessels, skin, skeletal muscle, heart, testis, ovarian epithelium, and bone marrow. In the bone marrow, several millions of new blood cells arise every day from blood-forming stem cells. Scientists have not been able to determine whether every mature organ includes stem cells. Tissue-specific stem cells are rare and often difficult to grow in culture and isolate. Of those, the blood-forming and hematopoietic stem cells residing in the bone marrow are the most studied.
Induced pluripotent stem cells (iPSCs) are cells engineered to become pluripotent, that is, capable of forming multiple types of cell types. Although human iPSCs open up an exciting window into stem cell research, this technology is still in its infancy, and many related crucial questions remain unanswered.
A promising avenue of stem cell research resides in the replacement of affected or damaged cells with healthy ones, an approach defined as regenerative medicine. This field has prompted scientists to investigate the use of fetal, embryonic, and adult stem cells derived from various specialized cell types—muscle, nerve, blood, and skin cells—to assess their use as potential treatment for various conditions.
However, it is important to keep in mind that in some instances, the immune system itself may be the source of so-called autoimmune diseases that damage vital cells, such as the ones producing insulin in type 1 diabetes patients.
The end goal of stem cell–based regenerative medicine—the restoration of the function of damaged or lost tissues and organs—can be achieved through different means such as the injection of stem cells engineered in the laboratory, or the administration of drugs susceptible of coaxing existing stem cells into carrying out a more efficient repair.
However, in spite of the encouraging prospects presented by potential stem cell therapies, there are challenges in the use of stem cells for regenerative purposes. In adult individuals, tissue-specific stem cells are rare and tend to be difficult to isolate. Additionally, while adult stem cells hold the promise of self-regeneration in animals and humans, the fact that they only exist in minute quantities creates some hurdles in the sense that they must be identified in sufficient numbers in order to be usable for therapy. All this makes it harder to conduct effective clinical studies. Researchers from various laboratories are currently attempting to find ways to grow and collect large enough quantities of adult stem cells susceptible to generate specific cell types.
Blood-forming stem cells make up only a tiny fraction of the bone marrow. Although, they can be isolated in the laboratory, these cells cannot be conserved for a long time. Some cells, such as skin stem cells, offer better expansion capabilities in the laboratory and are used for specific treatments like burns. Other types of stem cells, such as bone marrow cells, can be infused in the blood stream. Mesenchymal muscle and neural stem cells, on the other hand, present more challenging routes for administration. Another obstacle is the potential rejection by the immune system of stem cells originating from donors other than the patient. This sometimes leads to the need to harvest stem cells from the intended recipient of the related therapy.
Finally, an added drawback of adult stem cells is their relative age compared to embryonic stem cells, which makes them more susceptible to DNA abnormalities caused by toxins, random errors, or environmental factors.
All embryonic stem cells arise from young embryos and are usually genetically different from those of any potential recipient. They can therefore be rejected by the immune system, the reason why iPSCs collected from the patient’s cells through reprogramming constitutes such a major breakthrough.
A major advantage of pluripotent cells is that they can be grown and expanded indefinitely in the laboratory. Therefore, in contrast to adult stem cells, sheer quantity will be less of a limiting factor. Another advantage of these cells is the large number of different cell types present in a given organ that they can generate. This enables the development of a multitude of tissue-engineering approaches aimed at reconstructing a variety of organs in the lab.
Scientists are using many different methods of identification of adult stem cells. One of them is their labeling within a living tissue by means of molecular markers enabling the determination of the types of specialized cell they are susceptible to generate. Another procedure involves the extraction of cells from a living animal, their labeling in cell culture, and their transplantation into another animal to see whether these cells are restored inside their original tissue.
One of the major tasks confronting researchers is to demonstrate that a single adult stem cell is able to produce a series of genetically identical cells which, in turn, would give rise to differentiated cell types.
What do we currently know about stem cell differentiation? What are the pathways leading to such a process?
In living animals, and as needed, adult stem cells have the ability to divide and give rise to mature cell types that feature the functions, shapes, and specialized structures of a given tissue.
For instance, hematopoietic stem cells (HSCs) are known to produce all kinds of blood cells, including B or T lymphocytes, natural killer or red blood cells, basophils, neutrophils, eosinophils, macrophages, and monocytes.
On the other hand, neural stem cells located in the brain generate three major cell types: oligodendrocytes, astrocytes, and nerve cells, while skin stem cells that line up the base of hair follicles and the basal layer of the epidermis give rise to keratinocytes. In the lining of the digestive tract, epithelial stem cells are embedded in crypts and produce goblet, absorptive, entero-endocrine, and paneth cells.
Mesenchymal stem cells (MSCs)—multipotent skeletal stem cells, or stromal cells susceptible to differentiate into a variety of cell types—can give rise to a certain number of cell types, including bone cells (osteocytes and osteoblasts), fat cells (adipocytes), cartilage cells (chondrocytes), and stromal cells that are in support of blood formation.
Transdifferentiation is generally defined as “lineage reprogramming,” a process during which a mature somatic cell transmutes into another without going through an intermediate pluripotent state. The adult stem cell types involved may then differentiate into other types of cells located in tissues or organs, differing from those expected to derive from the original cells’ anticipated pedigree. One such example is blood-forming cells, capable of differentiating into cardiac muscle cells.
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