TY - JOUR
T1 - Fms-related tyrosine kinase 3 expression discriminates hematopoietic stem cells subpopulations with differing engraftment-potential
T2 - Identifying the most potent combination
AU - Huang, Yiming
AU - Ratajczak, Mariusz Z.
AU - Reca, Ryan
AU - Xu, Hong
AU - Tanner, Michael
AU - Rezzoug, Francine
AU - Hussain, Lala Rukh
AU - Fugier-Vivier, Isabelle
AU - Bolli, Roberto
AU - Ildstad, Suzanne T.
PY - 2008/4
Y1 - 2008/4
N2 - BACKGROUND. Fms-related tyrosine kinase 3 (Flt3)-ligand (FL) promotes the proliferation, differentiation, development, and mobilization of hematopoietic cells. We previously found that FL-mobilized hematopoietic stem cells (HSC) engraft efficiently, whereas FL-expanded bone marrow HSC do not. The function of FL-mobilized c-Kit Sca-1Lin (KSL) subpopulations has not been systematically evaluated. A precise definition of the repopulating ability is needed to define which HSC subpopulations are critical for long-term chimerism and tolerance induction. FL significantly mobilized c-Kit and c-Kit Sca-1Lin cells into peripheral blood (PB). Here, we evaluated the influence of Flt3 expression on long-term repopulating ability of HSC subpopulations. METHODS. c-Kit or c-Kit KSL cells were sorted from PB of FL-treated green fluorescent protein-positive donors. The function of these cells was evaluated using competitive reconstitution assays, colony-forming units spleen, and colony forming cell assays. The function of c-Kit CD34Flt3 KSL, c-Kit CD34Flt3 KSL, c-Kit CD34Flt3 KSL were investigated in an in vivo transplantation model. RESULTS. Only FL-mobilized PB c-Kit KSL cells exhibited high spleen colony-forming unit activity, generated high numbers of both lymphoid and myeloid colonies in vitro, and rescued ablated recipients. FL-mobilization expanded both c-Kit CD34Flt3 cells (short-term HSC) and c-Kit CD34Flt3 KSL cells (long-term HSC). There was a significant decrease in c-Kit CD34Flt3 KSL late multipotent progenitors in PB. A combination of c-Kit CD34Flt3 and c-Kit CD34Flt3 KSL cells offered the most effective rescue of ablated recipients. CONCLUSIONS. These data suggest that engraftment of purified HSC is influenced by both short- and long-term repopulating populations and that Flt3 expression may be useful for selecting the most critical HSC subpopulations for transplantation.
AB - BACKGROUND. Fms-related tyrosine kinase 3 (Flt3)-ligand (FL) promotes the proliferation, differentiation, development, and mobilization of hematopoietic cells. We previously found that FL-mobilized hematopoietic stem cells (HSC) engraft efficiently, whereas FL-expanded bone marrow HSC do not. The function of FL-mobilized c-Kit Sca-1Lin (KSL) subpopulations has not been systematically evaluated. A precise definition of the repopulating ability is needed to define which HSC subpopulations are critical for long-term chimerism and tolerance induction. FL significantly mobilized c-Kit and c-Kit Sca-1Lin cells into peripheral blood (PB). Here, we evaluated the influence of Flt3 expression on long-term repopulating ability of HSC subpopulations. METHODS. c-Kit or c-Kit KSL cells were sorted from PB of FL-treated green fluorescent protein-positive donors. The function of these cells was evaluated using competitive reconstitution assays, colony-forming units spleen, and colony forming cell assays. The function of c-Kit CD34Flt3 KSL, c-Kit CD34Flt3 KSL, c-Kit CD34Flt3 KSL were investigated in an in vivo transplantation model. RESULTS. Only FL-mobilized PB c-Kit KSL cells exhibited high spleen colony-forming unit activity, generated high numbers of both lymphoid and myeloid colonies in vitro, and rescued ablated recipients. FL-mobilization expanded both c-Kit CD34Flt3 cells (short-term HSC) and c-Kit CD34Flt3 KSL cells (long-term HSC). There was a significant decrease in c-Kit CD34Flt3 KSL late multipotent progenitors in PB. A combination of c-Kit CD34Flt3 and c-Kit CD34Flt3 KSL cells offered the most effective rescue of ablated recipients. CONCLUSIONS. These data suggest that engraftment of purified HSC is influenced by both short- and long-term repopulating populations and that Flt3 expression may be useful for selecting the most critical HSC subpopulations for transplantation.
KW - Flt3-ligand
KW - Hematopoietic stem cells
KW - Mobilization
KW - Transplantation
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UR - http://www.scopus.com/inward/citedby.url?scp=42549122617&partnerID=8YFLogxK
U2 - 10.1097/TP.0b013e31816a89cf
DO - 10.1097/TP.0b013e31816a89cf
M3 - Article
C2 - 18431239
AN - SCOPUS:42549122617
SN - 0041-1337
VL - 85
SP - 1175
EP - 1184
JO - Transplantation
JF - Transplantation
IS - 8
ER -