Submitted February 22, 2007
Accepted July 18, 2007
Establishment of transplantable porcine tumor cell lines derived from MHC inbred miniature swine
Patricia S Cho, Diana P Lo, Krzysztof J Wikiel, Haley C Rowland, Rebecca C Coburn, Isabel M McMorrow, Jennifer G Goodrich, J Scott Arn, Robert A Billiter, Stuart L Houser, Akira Shimizu, Yong-Guang Yang, David H Sachs, and Christene A Huang*
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
* Corresponding author; email: huangc{at}helix.mgh.harvard.edu.
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 MGH 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. Tissue samples were obtained for pathology, phenotyped by flow cytometry, and placed in culture. Based on growth, lines were selected for passage into NOD/SCID mice and miniature swine. Porcine tumor recipients were pre-conditioned with total body irradiation from 0 to 500cGy or with a 30-day course of oral cyclosporine. We identified nineteen cases of hematological tumors. Nine distinct tumor cell lines were established from eight of these cases, including three derived from highly inbred sublines. In vivo tumor growth and serial transfer was observed in immunocompromised mice for one tumor cell line and in miniature swine for one of two tumor cell lines expanded for this purpose. These results suggest the possibility of developing a transplantable tumor model in this large animal system.
