Hematopoietic stem cell expansion: challenges and opportunities.
Attempts to improve hematopoietic reconstitution and engraftment potential of ex vivo-expanded hematopoietic stem and progenitor cells (HSPCs) have been largely unsuccessful due to the inability to generate sufficient stem cell numbers and to excessive differentiation of the starting cell population. Although hematopoietic stem cells (HSCs) will rapidly expand after in vivo transplantation, experience from in vitro studies indicates that control of HSPC self-renewal and differentiation in culture remains difficult. Protocols that are based on hematopoietic cytokines have failed to support reliable amplification of immature stem cells in culture, suggesting that additional factors are required. In recent years, several novel factors, including developmental factors and chemical compounds, have been reported to affect HSC self-renewal and improve ex vivo stem cell expansion protocols. Here, we highlight early expansion attempts and review recent development in the extrinsic control of HSPC fate in vitro.
Department of Biology of Aging, Section Stem Cell Biology, European Research Institute for the Biology of Aging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Marta A
MA
Walasek
Ronald
R
van Os
Gerald
G
de Haan
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D005801:Genes, Homeobox; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D055153:Stem Cell Niche
D016207:Cytokines; D051880:Receptors, Notch