Chapter 067. Applications of Stem Cell Biology in Clinical Medicine (Part 1) ppt

Chapter 067. Applications of Stem Cell
Biology in Clinical Medicine
(Part 1)

Harrison's Internal Medicine > Chapter 67. Applications of Stem Cell
Biology in Clinical Medicine
Applications of Stem Cell Biology in Clinical Medicine: Introduction
Organ damage and the resultant inflammatory responses initiate a series of
repair processes, including stem cell proliferation, migration, and differentiation,
often in combination with angiogenesis and remodeling of the extracellular matrix.
Endogenous stem cells in tissues such as liver and skin have a remarkable ability
to regenerate the organs, whereas heart and brain have a much more limited
capability for self-repair. Under rare circumstances, circulating stem cells may
contribute to regenerative responses by migrating into a tissue and differentiating
into organ-specific cell types. The goal of stem cell therapies is to promote cell
replacement in organs that are damaged beyond their ability for self-repair.

Sources of Stem Cells for Tissue Repair
Different types of stem cells include embryonic stem (ES) cells, umbilical
cord blood stem cells, organ-specific somatic stem cells (e.g., neural stem cells for
treatment of the brain), and somatic stem cells capable of generating cell types
specific for the target rather than the donor organ (e.g., bone marrow
mesenchymal stem cells for cardiac repair) (Chap. 66).
ES cells self-renew endlessly so that a single cell line with carefully
characterized traits can generate large numbers of cells that can be
immunologically matched with potential transplant recipients. However, little is
currently known about the mechanisms that govern differentiation of these cells or
processes that limit their unbridled proliferation.
Human ES cells are difficult to culture and grow slowly. ES cells tend to
develop abnormal karyotypes and have the potential to form teratomas if they are
not committed to the desired cell types before transplantation. The study of human

ES cells has been controversial, and their use in clinical applications would be
unacceptable to some patients and physicians despite their enormous potential.
Somatic cell nuclear transfer ("therapeutic cloning") represents an alternative
method for creating ES cell lines that are genetically identical to the patient. It
may also be possible to derive pluripotent stem cells from spermatogonia in the
adult human testis, providing another strategy for obtaining genetically identical
stem cells.
Umbilical cord blood stem/progenitor cells are associated with less graft-
versus-host disease compared to marrow stem cells. They have less HLA
restriction than adult marrow stem cells, and they are less likely to be
contaminated with herpesvirus.
However, it is unclear how many different cell types these cells can
generate, and methods for differentiating them into nonhematopoietic phenotypes
are largely lacking. The quantity of cells from any single source can also be
limiting.
Organ-specific multipotent stem cells are already somewhat specialized and
may be easier to induce into desired cell types. These cells could potentially be
obtained from the patient and amplified in culture, thereby circumventing the
problems associated with immune rejection.
Multipotent stem cells are relatively easy to harvest from bone marrow
(Chap. 68) but are more difficult to isolate from other tissues, such as heart and
brain. Substantial efforts have therefore been devoted to obtaining more
pluripotent stem cell populations, such as bone marrow mesenchymal stem cells
(MSCs) or adipose stem cells, for use in regenerative strategies.
Tissue culture evidence suggests that these stem cell populations are able to
generate a variety of cell types, including myocytes, chondrocytes, tendon cells,
osteoblasts, cardiomyocytes, adipocytes, hepatocytes, and neurons, through a
process known as transdifferentiation.
However, it is unclear how effectively these differentiated cells integrate
into organs, survive, and function after transplantation in vivo. Early studies of

bone marrow–derived stem cells transplanted into heart, liver, and other organs
suggested that the cells had differentiated into organ-specific cell types.
Subsequent studies, however, revealed that the stem cells had fused with
cells resident in the organs. Further studies will be necessary to determine whether
transdifferentiation of MSCs or other stem cell populations occurs at a high
enough frequency to be useful for stem cell replacement therapy.
Regardless of the source of the stem cells used in regenerative strategies, a
number of generic problems must be overcome for the development of successful
clinical applications.
These include development of methods for reliably generating large
numbers of specific cell types, minimizing the risk of tumor formation or
proliferation of inappropriate cell types, ensuring the viability and function of the
engrafted cells, overcoming immune rejection when autografts are not used, and
facilitating revascularization of the regenerated tissue. Each organ system will also
pose tissue-specific problems for stem cell therapies.