Stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and continue to proliferate to produce more of the same stem cells. Stem cells are found in both embryonic and adult organisms. These cells have the unique ability to self-renew or to differentiate into various cell types in response to signals within the body. These properties provide stem cells with the capability for tissue repair, replacement and regeneration.
In the embryo, stem cells differentiate into all the body’s cell types making them pluripotent. This includes the three germ layers of the ectoderm, mesoderm and endoderm.
In the adult, stem cells are found in select locations such as the bone marrow and adipose tissue. They exist to replenish lost cell types and are considered multipotent since they can only differentiate into a few cell types. In mammals, types of stem cells are the hematopoietic stem cells which replenish blood and blood products, basal stem cells which maintain skin and mesenchymal stem cells which maintain bone, cartilage, muscle fate and connective tissue. These are a few types of stem cells but there are others.
Properties of a stem cell requires,
- Self- renewal which is the ability to go through growth and division while maintaining the undifferentiated state.
- Potency which is the capacity to differentiate into specialized cell types. This definition would require all stem cells to be either totipotent or pluripotent which either could replace any type of cell. However, multipotent stem cells have been found to differentiate into other types of cells. For example, mesenchymal stem cells have been found to differentiate into other cell types of not just skin, bone, cartilage, connective tissue.
- Stem cells have unlimited self-renewal capabilities.
- Stem cells are non-differentiated with unspecialized function.
- When signaled, stem cells can differentiate into specific cell types under appropriate conditions.
Self -Renewal Function
Asymmetric cell division: a stem cell divides into one cell which is identical to itself and a daughter cell which is differentiated.
When a stem cell self-renews, the division does not disrupt the undifferentiated state of the cell. The demands of the cell cycle are maintained such as the upkeep of multipotency or pluripotency.
Stochastic differentiation is when one stem cell divides into two daughter cells, another stem cell undergoes division and produces stem cells identical to the original.
Potency specifies the differentiation potential into different cell types. There are 5 recognized potency classifications,
- Totipotent or Omnipotent stem cells can differentiate and as such, can divide and create a complete viable organism. These cells are formed by the fusion of the sperm and egg to generate an embryo.
- Pluripotent stem cells can differentiate into nearly all cell types.
- Multipotent stem cells can differentiate into several cell types typically closely related to a specific family of tissue types.
- Oligopotent stem cells can differentiate into only a few cell types such as lymphoid or myeloid cells.
- Unipotent cells can only produce one type of cell.
Sources of Stem Cells
Generally, there are three recognized sources of stem cells, fetal or amniotic, adult and induced pluripotent.
Multipotent Stem Cells
This category adult stem cells that demonstrate the ability to self- renew or differentiate into specialized cell types present in a specific tissue or organ. Examples include hematopoietic stem cells that specialize in blood cells, mesenchymal stem cells that give rise to osteoblasts, myocytes, chondrocytes and adipocytes and neural stem cells which differentiate into neurons, astrocytes and oligodendrocytes.
These cells are present in specialized tissues and act primarily to replenish damaged or apoptotic cells. They remain until signaled to differentiate.
Pluripotent Stem Cells
Pluripotent stem cells have the ability to differentiate into any cell type. They are classified into embryonic origin and induced pluripotent stem cells.
Embryonic stem cells are derived from embryos. Cells taken in the first four cleavages are considered totipotent. Although a rich source of stem cells, the use of embryos has ethical challenges.
Umbilical cord stem cells are the most widely used pluripotent stem cells. Since this tissue is discarded, there are no ethical issues and can be used in a wide variety of clinical applications.
Induced pluripotent stem cells are adult cells reprogrammed in the lab to behave like embryonic stem cells. The advantage is the reduced chances of graft rejection since it uses cells from the same source.
Mesenchymal Stem Cells
Mesenchymal stem cells can be isolated from adult or fetal tissue and membranes. Sources include fat, bone marrow, umbilical cord tissue, placenta and muscle.
Due to their fibroblastic morphology, they provide support and structure in different organs and tissues. Mesenchymal stem cells possess the ability to differentiate into several cell types from the mesodermal germ layer including adipocytes, osteocytes and chondrocytes. Studies have also proven the differentiation has extended to other germ layers such as embryonic germ layers. Neurons and hepatocytes have been shown to originate from MSC in lab analysis. However, this is controversial since it has not been proven in vivo.
The plasticity of mesenchymal stem cells makes them the most important cell type for regenerative medicine. Their advantages for clinical application include easy isolation, high yield, high plasticity and the ability to mediate inflammation. MSC promote proliferation, cell growth and remodeling. There are no ethical implications with their use and MSC do not form teratomas ensuring safety.
Adipose tissue is rich in MSC and at least 100- fold greater yield than bone marrow. However, the harvest is still an invasive procedure.
Besides being classified as multipotent, mesenchymal stem cells express a relatively high level of pluripotent markers related to embryological stem cells. These markers are involved in the regulation of the multipotency, self -renewal and overall proliferation of these cells.
This could explain the multipotency/pluripotency of MSC.
Induced Pluripotency Cells iPS
The iPS cells are generated from the induction of expression of transcription factors associated with pluripotency allowing a differentiated somatic cell to reverse to the embryonic stage.
The discovery of such technology was based on the hypothesis that nuclear reprogramming is driven by factors that play a critical role in maintaining the pluripotency of ESC.
This field has been growing exponentially in the last few years. This field depends on the integration of transgenes and several techniques have been developed to improve the quality of the generated MSC.
Adipose derived stem cells are naturally multipotent and acquire pluripotency after induction by these methods.
Although this field is rapidly expanding and quite interesting, pluripotent cells are easily obtained from amniotic sources.
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