ES-cell derived hematopoietic cells induce transplantation tolerance.
BACKGROUND
Bone marrow cells induce stable mixed chimerism under appropriate conditioning of the host, mediating the induction of transplantation tolerance. However, their strong immunogenicity precludes routine use in clinical transplantation due to the need for harsh preconditioning and the requirement for toxic immunosuppression to prevent rejection and graft-versus-host disease. Alternatively, embryonic stem (ES) cells have emerged as a potential source of less immunogenic hematopoietic progenitor cells (HPCs). Up till now, however, it has been difficult to generate stable hematopoietic cells from ES cells.


RESULTS
Here, we derived CD45(+) HPCs from HOXB4-transduced ES cells and showed that they poorly express MHC antigens. This property allowed their long-term engraftment in sublethally irradiated recipients across MHC barriers without the need for immunosuppressive agents. Although donor cells declined in peripheral blood over 2 months, low level chimerism was maintained in the bone marrow of these mice over 100 days. More importantly, chimeric animals were protected from rejection of donor-type cardiac allografts.


CONCLUSIONS
Our data show, for the first time, the efficacy of ES-derived CD45(+) HPCs to engraft in allogenic recipients without the use of immunosuppressive agents, there by protecting cardiac allografts from rejection.
Bonde
Sabrina
S
Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa, United States of America.
Chan
Kun-Ming
KM
Zavazava
Nicholas
N
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D002469:Cell Separation; D053595:Embryonic Stem Cells / Q000166:cytology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006084:Graft Rejection / Q000517:prevention & control; D016027:Heart Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D051379:Mice; D008954:Models, Biological; D014157:Transcription Factors / Q000378:metabolism; D023001:Transplantation Tolerance / Q000276:immunology*
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018398:Homeodomain Proteins; C513262:Hoxb4 protein, mouse; D007166:Immunosuppressive Agents; D014157:Transcription Factors; D017493:Leukocyte Common Antigens
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