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Pig to monkey bone marrow and kidney xenotransplantation
T Sablinski1, P R Gianello, M Bailin
1Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA.
Surgery
|April 1, 1997
Summary
This study shows that a protocol involving lymphohematopoietic chimerism and natural antibody removal can prevent hyperacute rejection in pig-to-primate kidney transplants, achieving short-term graft survival and donor cell engraftment.
Area of Science:
- Transplantation immunology
- Xenotransplantation
- Immunosuppression strategies
Background:
- Discordant xenograft rejection poses significant challenges for long-term survival.
- Established methods focus on lymphohematopoietic chimerism and eliminating preformed natural antibodies (nAbs) to induce tolerance.
Purpose of the Study:
- To evaluate a protocol for inducing tolerance in discordant xenotransplantation.
- To assess the efficacy of lymphohematopoietic chimerism and nAb removal in preventing xenograft rejection.
Main Methods:
- Conducted 11 porcine to nonhuman primate kidney transplantations.
- Experimental group received induction therapy: irradiation, anti-thymocyte globulin, thymic irradiation, and pig bone marrow infusion.
- Natural antibodies were removed via pig liver perfusion or Gal-alpha(1,3)-Gal adsorption columns prior to transplantation.
Main Results:
- Effective removal of IgM and IgG nAbs was confirmed by flow cytometry.
- Experimental group maintained low nAb titers; control group showed increased titers.
- Longest surviving recipient showed excellent kidney function for 15 days, with evidence of short-term pig bone marrow cell engraftment (3% at day 7, 30% myeloid progenitors at day 14).
Conclusions:
- The protocol effectively prevents hyperacute rejection and maintains xenograft function for up to 15 days.
- Short-term engraftment of xenogeneic bone marrow cells is achievable in this discordant large animal model.
- Further studies are needed to determine if this engraftment can induce long-term tolerance.