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PMID: 18033883 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Efficient transplantation via antibody-based clearance of hematopoietic stem cell niches.

Science (New York, N.Y.) ·Vol. 318 ·No. 5854 ·2007-11-23 ·Pages 1296-9

Czechowicz A, Kraft D, Weissman IL, Bhattacharya D

Abstract

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.

MeSH Terms
Animals Antibodies, Monoclonal/administration & dosage,blood,immunology Bone Marrow Cells/cytology Bone Marrow Transplantation Cell Proliferation Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells/cytology,physiology Mice Proto-Oncogene Proteins c-kit/immunology Spleen/cytology Time Factors Transplantation Chimera Transplantation Conditioning/methods
Chemicals
Antibodies, Monoclonal Proto-Oncogene Proteins c-kit
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Czechowicz Agnieszka
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
Weissman Irving L
Bhattacharya Deepta
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1149726
Published
2007-11-23
Pages
1296-9
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2527021
Subset
IM
Grants
NHLBI NIH HHS · K08 HL076335-02 · United States
NIAID NIH HHS · T32 AI007290 · United States
NHLBI NIH HHS · K08 HL076335-01A2 · United States
NHLBI NIH HHS · R01 HL058770-06 · United States
NHLBI NIH HHS · 5K08HL076335 · United States
NIDDK NIH HHS · K01 DK078318 · United States
NIDDK NIH HHS · 5K01DK078318 · United States
NHLBI NIH HHS · 5R01HL058770 · United States
NCI NIH HHS · R01 CA086065-06 · United States
NHLBI NIH HHS · R01 HL058770-07 · United States
NCI NIH HHS · 5R01CA086065 · United States
NCI NIH HHS · R01 CA086065-08 · United States
NHLBI NIH HHS · K08 HL076335-03 · United States
NIAID NIH HHS · T32AI0729022 · United States
NCI NIH HHS · R01 CA086065 · United States
NIDDK NIH HHS · K01 DK078318-01 · United States
NHLBI NIH HHS · R01 HL058770-08 · United States
NCI NIH HHS · R01 CA086065-07 · United States
NHLBI NIH HHS · R01 HL058770 · United States
External Links
PubMed source DOI: 10.1126/science.1149726 PMC Full Text View journal details
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