Evaluation of Histocompatibility after SLA-Matched Kidney Allo-Transplantation in Cloned Miniature Pigs

Abstract

Purpose: Immunological and histological compatibility in kidney transplantation between genetically identical somatic cell-cloned miniature pigs. Materials and methods: Eight out-bred domestic swine and eight genetically identical cloned miniature pigs were used. Donor-recipient pairs were chosen according to RBC or lymphocyte cross match by flow cytometry, and swine leukocyte antigen (SLA) genotyping. We examined hypervariable region 1 (HV1) of mitochondrial DNA (mtDNA). Kidney transplantation was performed in four different groups as followings: auto-transplantation, out-bred allo-transplantation, different somatic cell cloned allo-transplantation, and same somatic cell cloned allo-transplantation. Kidney function was daily evaluated after transplantation and in the case of rejection renal grafts were harvested for histology prior to euthanasia. Results: The mtDNA sequence of the HV1 region was found to be variant among genetically identical cloned miniature pigs. Accelerate acute rejection was observed in all three allograft pairs. Although delayed increase in plasma creatinine and urea nitrogen, and less characteristic lesions of mononuclear cell infiltration were observed, the general pattern of all-rejection episode was shown in the same somatic cell-cloned pigs. Conclusions: The results suggest that genetically identical somatic cell nuclear transfer (SCNT) cloned miniature pigs were immunologically incompatible with one another in renal allo-transplantation despite matched SLA. Other allo-antigens including minor histocompatibility antigen encoded by mt DNA might be related to the outcome. This work was supported by a grant from the Next-Generation BioGreen 21 Program (No.PJ008032), from BioGreen 21 Program, Rural Development Administration, Republic of Korea.