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Article
Nature Medicine  8, 171 - 178 (2002)
doi:10.1038/nm0202-171

Preimplantation-stage stem cells induce long-term allogeneic graft acceptance without supplementary host conditioning

Fred Fändrich1, 7, Xiongbin Lin1, 7, Gui X. Chai2, 3, Maren Schulze1, Detlev Ganten2, Michael Bader2, Julia Holle1, Dong-Sheng Huang1, Reza Parwaresch4, Nicholaus Zavazava5 & Bert Binas2, 6

1  Department of General Surgery and Thoracic Surgery, University of Kiel, 24105 Kiel, Germany

2  Max-Delbrück-Center for Molecular Medicine (MDC), 13092 Berlin, Germany

3  BML 116, Pathology Department, Yale University School of Medicine New Haven, Connecticut 06520-8023, USA

4  Institute of Hematopathology, University of Kiel, 24105 Kiel, Germany

5  University Iowa Hospitals and Clinics &VA Medical Center, Iowa City, Iowa, USA

6  Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, Texas, USA

7  F.F. and X.L contributed equally to this study.

Correspondence should be addressed to Fred Fändrich ffaendrich@surgery.uni-kiel.de
Hematopoietic stem cells have been successfully employed for tolerance induction in a variety of rodent and large animal studies. However, clinical transplantation of fully allogeneic bone marrow or blood-borne stem cells is still associated with major obstacles, such as graft-versus-host disease or cytoreductive conditioning-related toxicity. Here we show that when rat embryonic stem cell-like cells of WKY origin are injected intraportally into fully MHC-mismatched DA rats, they engraft permanently (>150 days) without supplementary host conditioning. This deviation of a potentially alloreactive immune response sets the basis for long-term graft acceptance of second-set transplanted WKY cardiac allografts. Graft survival was strictly correlated with a state of mixed chimerism, which required functional thymic host competence. Our results provide a rationale for using preimplantation-stage stem cells as vehicles in gene therapy and for the induction of long-term graft acceptance.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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