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

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 C

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