Chapter 067. Applications of Stem Cell
Biology in Clinical Medicine
(Part 2)

Strategies for Stem Cell Replacement
Stem cell transplantation is not a new concept and it is already part of
established medical practice. Hematopoietic stem cells (HSCs) (Chap. 68) are
responsible for the long-term repopulation of all blood elements in bone marrow
transplant recipients. HSC transplantation is now the gold standard against which
other stem cell transplantation therapies will be measured. Transplantation of
differentiated cells is also a clinical reality, as donated organs (e.g., liver, kidney)
and tissues (i.e., cornea, eye, skin) are often used to replace damaged tissues.
However, the clinical need for transplantable tissues and organs far outweighs the
available supply, and organ transplantation has limited potential for some tissues
such as the brain. Stem cells offer the possibility of a renewable source of cell
replacement for virtually all organs.
At least three different therapeutic concepts for cell replacement have been
considered (Fig. 67-1): (1) injection of stem cells directly into the damaged organ
or into the circulation, allowing them to "home" into the damaged tissue; (2) in
vitro differentiation of stem cells followed by transplantation into a damaged
organ—e.g., pancreatic islet cells could be generated from stem cells prior to
transplantation into patients with diabetes, whereas cardiomyocytes could be
generated to treat ischemic heart disease; and (3) stimulation of endogenous stem
cells to facilitate repair—e.g., administration of appropriate growth factors to
amplify numbers of endogenous stem/progenitor cells or direct them to
differentiate into the desired cell types. In addition to these strategies for cell
replacement, the ex vivo or in situ generation of tissues provides an alternative
means of tissue engineering (Chap. 69). Stem cells are also excellent vehicles for
cellular gene therapy (Chap. 65).
Figure 67-1


are not derived from direct generation of cardiomyocytes but rather from indirect
effects of the stem cells on resident cells. This may reflect the release of soluble
growth factors, induction of angiogenesis, or some other mechanism.