Efficient Transplantation via Antibody-Based Clearance of Hematopoietic Stem Cell Niches

• DOI: 10.1126/science.1149726
• Publication Date: 2007-11-22T19:43:02Z
• Authors: Agnieszka Czechowicz; Daniel Kraft; Irving L. Weissman; Deepta Bhattacharya
• Keywords: Transplantation Chimera; 0303 health sciences; Time Factors; Transplantation Conditioning; Hematopoietic Stem Cell Transplantation; Antibodies, Monoclonal; Bone Marrow Cells; Hematopoietic Stem Cells; 3. Good health; Mice; Proto-Oncogene Proteins c-kit; 03 medical and health sciences; Animals; Spleen; Bone Marrow Transplantation; Cell Proliferation

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.