Background

All of the methodologies discussed on this website involve the usage of adult somatic or embryonic stem cells as vehicles for the products of transduced genes. As such, an understanding of the acquisition and dynamics of human stem cells is requisite for comprehension.

Stem cells are characterized by the ability to renew themselves and to give rise to specialized cells. There are two general types of naturally occurring stem cells: those which are found in embryonic tissue and those found in differentiated tissue. These are referred to as embryonic and adult stem cells, respectively. Embryonic stem cells are capable of reproducing indefinitely in culture and differentiating into any cell type, whereas adult stem cells can renew themselves only for a limited period of time and can differentiate to yield the specialized cell type of the tissue from which it originated.

Embryonic stem cells are derived from the cells of the inner cell mass of a blastocyst. The inner cell mass is capable of forming all three germ layers of the embryo (endoderm, mesoderm, and ectoderm) which each generate specific tissues of the body. Adult stem cells are generally tissue specific. For example, mesenchymal stem cells may be derived from adipose tissue, hematopoietic stem cells from blood, and neural stem cells from brain tissue. Because they are derived from tissues which have already undergone some degree of differentiation, some of these stem cells have demonstrated reduced pluripotency as compared to embryonic stem cells and the differences between these cell types is not yet clearly understood.

It has also been shown in culture that adult stem cells do not exhibit the same degree of unlimited self-replication that embryonic stem cells do. It has been suggested that the reason behind this difference is due to the fact that embryonic stem cells exhibit chromosomes with particularly long telomeres. Because replication of cells causes truncation of chromosomal telomeres by 50-200 basepairs each round and thus results in senescence over time, these longer telomeres provide greater replication potential. It has also been hypothesized that embryonic stem cells can replicate indefinitely due to telomerase expression which continually adds telomere basepairs and thus negates the effects of chromosomal truncation.(6)

Perhaps the largest impediment in the clinical usage of stem cells is their source. The usage of embryonic stem cells collected from frozen embryos in fertility clinics is fraught with moral dilemma and has thus lead to a large push toward finding alternate stem cell sources. In this vein, it has been shown that adult stem cells exhibit varying degrees of plasticity and can therefore provide an adequate degree of pluripotency. Bone marrow derived mesenchymal stem cells are particularly attractive as they have been shown to give rise to virtually all cell types and thus demonstrate that the assumption that adult stem cells can only differentiate into the tissue in which they originally reside is questionable.(7) This is advantageous because adult stem cells are generally simple to collect, offer immediate autologous availability, and do not have any associated moral complications.

Another option for collection of stem cells which has garnered much attention recently is the usage of induced pluripotent stem cells. These are adult cells which have dedifferentiated into a more primitive state by the introduction of additional genes via a retrovirus. Although this technique originally involved the introduction of two oncogenes (c-Myc and Klf4) and thus made clinical usage questionable, other groups have recently achieved the same result without the use of these genes and have therefore opened the door to a much greater degree of stem cell collection simplicity.(8)(9) Thus although the field of stem cell research requires a greater understanding of stem cell collection and differentiation dynamics, recent developments have made their widespread clinical application much more likely.