Portal de Periódicos da CAPES

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

2007; American Association for the Advancement of Science; Volume: 318; Issue: 5854 Linguagem: Inglês

10.1126/science.1149726

1095-9203

Agnieszka Czechowicz, Daniel Kraft, Irving L. Weissman, Deepta Bhattacharya,

Immunotherapy and Immune Responses

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.