Embryonic and adult stem cells hold great promise for the treatment of disease and the rejuvenation of aging tissues—a concept that captures the imagination and hopes of the scientific and medical communities. No area of research focus since gene therapy evokes such enthusiasm among scientists and physicians but, nevertheless, raises ethical controversies as well. Proposed to be the ultimate cure for degenerative diseases of aging and a solution for the shortage of donated organs for transplantation, stem cells may even unlock the mysteries of early human development while providing the fountain of youth for an aging society. This chapter reviews the current state of knowledge, the controversies generated by stem cell research, and their application to diseases of aging.
Two basic types of stem cells exist: embryonic and adult. They are characterized by their ability to renew themselves for an indefinite period of time, as well as the ability to divide to create a differentiated cell type while remaining undifferentiated. In the adult, these self-renewing cell types are found in many tissues within a niche that provides a microenvironment that signals to renew the stem cell population or signals to induce unidirectional differentiation.
Depending upon the source of the stem cell, the differentiative potential of embryonic and adult stem cells varies. Fertilized oocytes and blastomeres (up to the eight-cell stage embryo) are described as being totipotent with the potential to differentiate and generate a complete organism. In contrast, embryonic stem cells (derived from the inner cell mass (ICM) of a blastocyte (see Figure 45.1) share the property of self-renewal and can differentiate into cells and tissues from any of the three germ layers. These cells are pluripotent, but not totipotent (these cells cannot form a placenta). As cells progress along the various steps of differentiation, they become less able to exhibit plasticity or to differentiate into cells of different lineages.
Thus, although the pluripotent embryonic stem cell has the capacity to become any cell type, adult stem cells are multipotent and persist into adulthood forming cells of the tissue in which they reside. These adult stem cells are responsible for the regenerative potential of the gastrointestinal, integumentary, spermatogenic, and hematopoietic systems. For example, spermatogonial stem cells (located near the basement membrane of the seminiferous tubules surrounded by Sertoli cells) can rejuvenate spermatogenesis following a gonadotoxic insult. Likewise, adult stem cells isolated from the liver, pancreas, kidney, and nervous system exhibit varying regenerative potential.
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