title: Increasing hematopoietic stem cell yield to develop mice with human immune systems.
abstract: Hematopoietic stem cells (HSCs) are unique in their capacity to give rise to all mature cells of the immune system. For years, HSC transplantation has been used for treatment of genetic and neoplastic diseases of the hematopoietic and immune systems. The sourcing of HSCs from human umbilical cord blood has salient advantages over isolation from mobilized peripheral blood. However, poor sample yield has prompted development of methodologies to expand HSCs ex vivo. Cytokines, trophic factors, and small molecules have been variously used to promote survival and proliferation of HSCs in culture, whilst strategies to lower the concentration of inhibitors in the culture media have recently been applied to promote HSC expansion. In this paper, we outline strategies to expand HSCs in vitro, and to improve engraftment and reconstitution of human immune systems in immunocompromised mice. To the extent that these "humanized" mice are representative of the endogenous human immune system, they will be invaluable tools for both basic science and translational medicine.
authors.affiliation: Regenerative Medicine Institute, Cedars-Sinai Medical Center, Room 361, Steven Spielberg Building, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Biancotti
authors.forename: Terrence
authors.initials: T
authors.lastname: Town
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation; D002470:Cell Survival; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology; D006680:HLA Antigens / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007107:Immune System / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D057170:Translational Research, Biomedical
chemical_list: D006680:HLA Antigens