Transplantation of human hematopoietic repopulating cells: mechanisms of regeneration and differentiation using human???mouse xenografts
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PURPOSE OF REVIEW: Some of the common clinical applications of hematopoietic stem cell (HSC) transplantation are used for treatment of leukemic malignancies, bone marrow/hematopoietic failure, and immunodeficiencies. Several inherent limitations of this procedure have restricted its use, including failed recipient bone marrow recovery and tumor relapse. Experimentally, ex-vivo manipulations and in-vivo xenotransplant assays used as clinical surrogates of HSC transplantation aim to improve quality and number of donor cells by uncovering the cellular and molecular mechanisms controlling HSC proliferation and differentiation upon transplantation. RECENT FINDINGS: One of the major research goals in hematopoietic stem cell transplant biology is the manipulation of factors affecting self-renewal, mobilization, and homing/retention of donor cells in the recipient. Transgenic systems in the mouse are frequently used as tools to dissect the individual pathways that influence these properties. Recently, identification of factors and chemicals that target HSCs or their 'niche', a supportive microenvironment for these stem cells in the bone marrow, has become a new avenue of interest to develop a novel therapeutic approach for enhancing HSC repopulation ability and engraftment efficiency. SUMMARY: This review focuses on recent progress in HSC ex-vivo manipulation and transplant biology, and the potential improvements arising from identification of molecular players and cellular components of the microenvironment niche.
