Stem cells are unspecialized cells which have the ability to replenish themselves (self-renew) and can give rise to one or more specialized cell types (differentiate). Stem cells vary in their differentiation capacity and can be classified according to their grade of plasticity as totipotent, pluripotent, multipotent and unipotent. As they differentiate, their differentiation potential becomes more restricted.
1) Totipotent stem cells have the biggest versatility from all the other stem cell types. In mammals, the fertilized egg and up to 4-8 cell stage blastomeres can be considered totipotent, meaning that they can give rise to an entire organism, including extra-embryonic tissues.
2) Embryonic stem cells (ESCs) are derived from the inner cell mass which gives rise to the embryo itself (Evans and Kaufman, 1981; Thomson et al., 1998). ESCs are pluripotent in that they have the potential to give rise to all three germ layers: endoderm, mesoderm or ectoderm, but unlike totipotent stem cells they cannot give rise to extra-embryonic tissues.
3) Multipotent stem cells have an even more limited differentiation potential and they can give rise to multiple cell types, preferably within a given lineage. Examples are hematopoietic stem cells which they can give rise to white blood cells, red blood cells and platelets.
4) Unipotent stem cells, or progenitor cells, can differentiate into only one cell type. Erythroid progenitor cells are one of the many types of unipotent stem cells which exist in the body (Martinez-Agosto et al., 2007; Serafini and Verfaillie, 2006).
There can be two sources of stem cells that can be used during their clinical application– Autologous and Allogenic. Autologous embryonic stem cells generated through therapeutic cloning and highly plastic adult stem cells from the umbilical cord blood or bone marrow are promising candidates. Allogenic stem cells can be derived from marrow, peripheral blood, cord blood of family donors or HLA typed or untyped unrelated donors. Isolation of cells from an autologous source and transplanting them to the damaged area (as in skin and bone grafting and autologous chondrocyte transplantation) is a good option, but it is associated with drawbacks like donor site morbidity and limited availability of amount of donor tissue, and unsuitability of using autologous tissue under certain situations such as renal failure and whole body radiation exposure. Thus, allogeneic cells/tissues have been used for transplant.
Political and ethical controversy surrounds the use of embryonic stem (ES) cells, and significant biological and regulatory concerns limit their clinical use (the latter concern also applies to induced pluripotent stem cells. Apart from the moral and political controversies, ES cells are by their derivation allogeneic in nature and subject to immune rejection if used in vivo. Although ES cells may of themselves lack HLA expression, the mature tissues that arise from these cells do express HLA antigens and are subject to immune surveillance. Furthermore, ES cells are prone to give rise to teratoma formation when placed in vivo, making their clinical use problematic if not impossible. Although iPS cell generation avoids the allogenicity issue, the teratoma formation problem is still present. Investigators have tried to avoid this issue by deriving mature tissues from iPS cells for clinical use. However, this process is time consuming and expensive. It should be noted that having tissues that escape immune surveillance is not desirable, as viral infections could go unchecked leading to viremia and serious consequences.
Multipotent stem cells are also known as somatic or adult stem cells. They are found in virtually all tissues and one possible function is to replenish cells that have died or lost their function, throughout an individual’s life. They have been identified in many different tissue types such as muscle, liver, bone marrow, umbilical cord, adipose tissue, retina, pancreas, central nervous system, dental pulp, blood, intestine and skin. Previously, it was thought that adult stem cells were restricted in their differentiation potential, giving rise only to cell types limited in their tissue of origin. Studies over the past years however suggest that adult stem cells from some tissues have the ability to differentiate into cell types from all three germ layers (Keating, 2006; Serafini and Verfaillie, 2006). This has caused great excitement, since they provide an easily accessible source of cells that could potentially treat degenerative diseases. Most adult tissues contain multipotent stem cells that can give rise to organ or tissue specific lineages, including the brain, heart, lung, intestine, muscle, adipose tissue, skin and teeth. The only two defining characteristics of these stem cells are their ability to self-renew and their capacity to differentiate into more specialized cell types; whereas the differences between different stem cell populations can be great and can significantly impact their potential for use in regenerative medicine. The best characterized and clinically most advanced are hematopoietic stem cells and mesenchymal stem cells.