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. Tissue samples were obtained for pathology, phenotyped by flow cytometry, and placed in culture. Based on growth, lines were selected for passage into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice and miniature swine. Porcine tumor recipients were preconditioned with total body irradiation from 0 to 500 cGy or with a 30-day course of oral cyclosporine. We identified 19 cases of hematologic tumors. Nine distinct tumor cell lines were established from 8 of these cases, including 3 derived from highly inbred sublines. In vivo tumor growth and serial transfer were observed in immunocompromised mice for one tumor cell line and in miniature swine for 1 of 2 tumor cell lines expanded for this purpose. These results suggest the possibility of developing a transplantable tumor model in this large-animal system.
Cho
Patricia S
PS
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Lo
Diana P
DP
Wikiel
Krzysztof J
KJ
Rowland
Haley C
HC
Coburn
Rebecca C
RC
McMorrow
Isabel M
IM
Goodrich
Jennifer G
JG
Arn
J Scott
JS
Billiter
Robert A
RA
Houser
Stuart L
SL
Shimizu
Akira
A
Yang
Yong-Guang
YG
Sachs
David H
DH
Huang
Christene A
CA
D000818:Animals; D045744:Cell Line, Tumor / Q000473:pathology; D016572:Cyclosporine / Q000494:pharmacology; D019337:Hematologic Neoplasms / Q000235:genetics / Q000473:pathology / Q000662:veterinary; D006649:Histocompatibility Antigens / Q000235:genetics; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007178:Inbreeding; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D013552:Swine; D013553:Swine Diseases / Q000473:pathology; D013556:Swine, Miniature / Q000235:genetics; D014916:Whole-Body Irradiation
D006649:Histocompatibility Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine
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