Hematopoietic development from human embryonic stem cell lines.
The most common human cell-based therapy applied today is hematopoietic stem cell (HSC) transplantation. Currently, human bone marrow, mobilized peripheral blood, and umbilical cord blood represent the major sources of transplantable HSCs, but their availability for use is limited by both compatibility between donor and recipient and required quantity. Although increasing evidence suggests that somatic HSCs can be expanded to meet current needs, their in vivo potential is concomitantly compromised after ex vivo culture. In contrast, human embryonic stem cells (hESC) possess indefinite proliferative capacity in vitro and have been shown to differentiate into the hematopoietic cell fate, giving rise to erythroid, myeloid, and lymphoid lineages using a variety of differentiation procedures. Human ESC-derived hematopoietic cells emerge from a subset of embryonic endothelium expressing PECAM-1, Flk-1, and VE-Cadherin, but lacking CD45 (CD45negPFV). These CD45negPFV precursors are exclusively responsible for hematopoietic potential of differentiated hESCs. hESC-derived hematopoietic cells show similar clonogenic capacity and primitive phenotype to somatic sources of hematopoietic progenitors and possess limited in vivo repopulating capacity in immunodeficient mice, suggestive of HSC function. Here, we will review current progress in studies of hESC-derived hematopoietic cells and discuss the potential precincts and applications.
Wang
Lisheng
L
Krembil Center for Stem Cell Biology and Regenerative Medicine, Robarts Research Institute, London, Ontario, Canada.
Menendez
Pablo
P
Cerdan
Chantal
C
Bhatia
Mickie
M
D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D004622:Embryo, Mammalian / Q000166:cytology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology