Preimplantation-stage stem cells induce long-term allogeneic graft acceptance without supplementary host conditioning.
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.
Fändrich
Fred
F
Department of General Surgery and Thoracic Surgery, University of Kiel, 24105 Kiel, Germany. ffaendrich@surgery.uni-kiel.de
Lin
Xiongbin
X
Chai
Gui X
GX
Schulze
Maren
M
Ganten
Detlev
D
Bader
Michael
M
Holle
Julia
J
Huang
Dong-Sheng
DS
Parwaresch
Reza
R
Zavazava
Nicholaus
N
Binas
Bert
B
D000818:Animals; D001755:Blastocyst / Q000166:cytology; D018920:Coculture Techniques; D016332:Fetal Tissue Transplantation; D006085:Graft Survival / Q000276:immunology*; D006086:Graft vs Host Disease / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008285:Major Histocompatibility Complex; D051381:Rats; D011912:Rats, Inbred ACI; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000276:immunology; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000276:immunology*