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

Harrisons Internal Medicine Chapter 67. Applications of Stem Cell Biology in Clinical MedicineApplications 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...
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Chapter 067. Applications of Stem Cell Biology in Clinical Medicine (Part 1) Chapter 067. Applications of Stem Cell Biology in Clinical Medicine (Part 1) Harrisons Internal Medicine > Chapter 67. Applications of Stem CellBiology in Clinical Medicine Applications of Stem Cell Biology in Clinical Medicine: Introduction Organ damage and the resultant inflammatory responses initiate a series ofrepair 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 abilityto regenerate the organs, whereas heart and brain have a much more limitedcapability for self-repair. Under rare circumstances, circulating stem cells maycontribute to regenerative responses by migrating into a tissue and differentiatinginto organ-specific cell types. The goal of stem cell therapies is to promote cellreplacement 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, umbilicalcord blood stem cells, organ-specific somatic stem cells (e.g., neural stem cells fortreatment of the brain), and somatic stem cells capable of generating cell typesspecific for the target rather than the donor organ (e.g., bone marrowmesenchymal stem cells for cardiac repair) (Chap. 66). ES cells self-renew endlessly so that a single cell line with carefullycharacterized traits can generate large numbers of cells that can beimmunologically matched with potential transplant recipients. However, little iscurrently known about the mechanisms that govern differentiation of these cells orprocesses that limit their unbridled proliferation. Human ES cells are difficult to culture and grow slowly. ES cells tend todevelop abnormal karyotypes and have the potential to form teratomas if they arenot committed to the desired cell types before transplantation. The study of humanES cells has been controversial, and their use in clinical applications would beunacceptable to some patients and physicians despite their enormous potential.Somatic cell nuclear transfer (therapeutic cloning) represents an alternativemethod for creating ES cell lines that are genetically identical to the patient. Itmay also be possible to derive pluripotent stem cells from spermatogonia in theadult human testis, providing another strategy for obtaining genetically identicalstem cells. Umbilical cord blood stem/progenitor cells are associated with less graft-versus-host disease compared to marrow stem cells. They have less HLArestriction than adult marrow stem cells, and they are less likely to becontaminated with herpesvirus. However, it is unclear how many different cell types these cells cangenerate, and methods for differentiating them into nonhematopoietic phenotypesare largely lacking. The quantity of cells from any single source can also belimiting. Organ-specific multipotent stem cells are already somewhat specialized andmay be easier to induce into desired cell types. These cells could potentially beobtained from the patient and amplified in culture, thereby circumventing theproblems 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 andbrain. Substantial efforts have therefore been devoted to obtaining morepluripotent 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 togenerate a variety of cell types, including myocytes, chondrocytes, tendon cells,osteoblasts, cardiomyocytes, adipocytes, hepatocytes, and neurons, through aprocess known as transdifferentiation. However, it is unclear how effectively these differentiated cells integrateinto organs, survive, and function after transplantation in vivo. Early studies ofbone marrow–derived stem cells transplanted into heart, liver, and other organssuggested that the cells had differentiated into organ-specific cell types. Subsequent studies, however, revealed that the stem cells had fused withcells resident in the organs. Further studies will be necessary to determine whethertransdifferentiation of MSCs or other stem cell populations occurs at a highenough frequency to be useful for stem cell replacement therapy. Regardless of the source of the stem cells used in regenerative strategies, anumber of generic problems must be overcome for the developm ...