TY - JOUR
T1 - Efficient transplantation via antibody-based clearance of hematopoietic stem cell niches
AU - Czechowicz, Agnieszka
AU - Kraft, Daniel
AU - Weissman, Irving L.
AU - Bhattacharya, Deepta
PY - 2007/11/23
Y1 - 2007/11/23
N2 - Upon intravenous transplantation, hematopoietic stem cells (HSCs) can home to specialized niches, yet most HSCs fail to engraft unless recipients are subjected to toxic preconditioning. We provide evidence that, aside from immune barriers, donor HSC engraftment is restricted by occupancy of appropriate niches by host HSCs. Administration of ACK2, an antibody that blocks c-kit function, led to the transient removal of >98% of endogenous HSCs in immunodeficient mice. Subsequent transplantation of these mice with donor HSCs led to chimerism levels of up to 90%. Extrapolation of these methods to humans may enable mild but effective conditioning regimens for transplantation.
AB - Upon intravenous transplantation, hematopoietic stem cells (HSCs) can home to specialized niches, yet most HSCs fail to engraft unless recipients are subjected to toxic preconditioning. We provide evidence that, aside from immune barriers, donor HSC engraftment is restricted by occupancy of appropriate niches by host HSCs. Administration of ACK2, an antibody that blocks c-kit function, led to the transient removal of >98% of endogenous HSCs in immunodeficient mice. Subsequent transplantation of these mice with donor HSCs led to chimerism levels of up to 90%. Extrapolation of these methods to humans may enable mild but effective conditioning regimens for transplantation.
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U2 - 10.1126/science.1149726
DO - 10.1126/science.1149726
M3 - Article
C2 - 18033883
AN - SCOPUS:36448992228
SN - 0036-8075
VL - 318
SP - 1296
EP - 1299
JO - Science
JF - Science
IS - 5854
ER -