Journal
SCIENCE
Volume 318, Issue 5854, Pages 1296-1299Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1149726
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Funding
- NCI NIH HHS [R01 CA086065-07, R01 CA086065, R01 CA086065-06, 5R01CA086065, R01 CA086065-08] Funding Source: Medline
- NHLBI NIH HHS [R01 HL058770-07, K08 HL076335-03, R01 HL058770-08, 5R01HL058770, K08 HL076335-02, 5K08HL076335, K08 HL076335-01A2, R01 HL058770-06, R01 HL058770] Funding Source: Medline
- NIAID NIH HHS [T32AI0729022, T32 AI007290] Funding Source: Medline
- NIDDK NIH HHS [K01 DK078318-01, K01 DK078318, 5K01DK078318] Funding Source: Medline
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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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