Efficient transplantation via antibody-based clearance of hematopoietic stem cell niches.
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.
Czechowicz
Agnieszka
A
Institute of Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kraft
Daniel
D
Weissman
Irving L
IL
Bhattacharya
Deepta
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*
D000911:Antibodies, Monoclonal; D019009:Proto-Oncogene Proteins c-kit