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

Nat Med. 2002 Feb;8(2):171-8. doi: 10.1038/nm0202-171.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / cytology
  • Coculture Techniques
  • Fetal Tissue Transplantation*
  • Graft Survival / immunology*
  • Graft vs Host Disease / prevention & control
  • Heart Transplantation / immunology*
  • Hematopoietic Stem Cell Transplantation*
  • Lymphocyte Culture Test, Mixed
  • Lymphocytes / cytology
  • Lymphocytes / immunology
  • Major Histocompatibility Complex
  • Rats*
  • Rats, Inbred ACI
  • Rats, Inbred WKY
  • Rats, Sprague-Dawley
  • Spleen / immunology
  • Transplantation Chimera
  • Transplantation, Homologous / immunology*