Myelogenous leukemia in adult inbred MHC-defined miniature swine: a model for human myeloid leukemias.

This manuscript reports on five cases of spontaneous myelogenous leukemia, similar to human disease, occurring within highly inbred, histocompatible sublines of Massachusetts General Hospital (MGH) MHC-defined miniature swine. In cases where a neoplasm was suspected based on clinical observations, samples were obtained for complete blood count, peripheral blood smear, and flow cytometric analysis. Animals confirmed to have neoplasms were euthanized and underwent necropsy.

Establishment of transplantable porcine tumor cell lines derived from MHC-inbred miniature swine.

The lack of transplantable tumors has limited assessment of graft-versus-tumor effects following hematopoietic cell transplantation in clinically relevant large-animal models. We describe the derivation and characterization of porcine tumor cell lines with initial efforts of tumor transplantation using immunocompromised mice and highly inbred sublines of Massachusetts General Hospital major histocompatibility complex (MHC)-inbred miniature swine. Autopsies were performed routinely on swine that died unexpectedly or had suspicion of malignancy based on clinical symptoms or peripheral blood analysis.

Lack of cardiac differentiation in c-kit-enriched porcine bone marrow and spleen hematopoietic cell cultures using 5-azacytidine.

The adult spleen is a source of early hematopoietic stem cells (HSC). We therefore studied whether culturing spleen or bone marrow (BM) HSC in medium containing 5-azacytidine could induce a cardiac phenotype. c-kit enrichment and depletion of adult pig spleen and BM mononuclear cells were obtained by magnetic bead separation using biotinylated pig stem cell factor (c-kit ligand).

Effects of mycophenolate mofetil on cardiac allograft survival and cardiac allograft vasculopathy in miniature swine.

Background: Chronic rejection, as manifested by cardiac allograft vasculopathy, remains the leading cause of late graft failure in heart transplant recipients. Despite recent clinical trials, the efficacy of mycophenolate mofetil in preventing human cardiac allograft vasculopathy remains controversial. We investigated whether mycophenolate mofetil would prevent cardiac allograft vasculopathy and prolong cardiac allograft survival in our well-established miniature swine model of heart transplantation.

Posttransplant lymphoproliferative disease after allogeneic transplantation of the spleen in miniature swine.

Spleen transplantation (SpTx) was performed in miniature swine across full major histocompatibility complex barriers to study the tolerogenic effect of the spleen. This study describes the development of posttransplant lymphoproliferative disease (PTLD) after allogeneic SpTx. Recipient pigs underwent whole body irradiation (100 cGy), thymic irradiation (700 cGy), and native splenectomy (day 0), and received a 45-day course of intravenous cyclosporine (trough level 400-800 ng/ml).