A NOVEL APPROACH TO GERM-LIINE PRESERVATION IN MACAQUES

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The non-human primate is a highly relevant model of human disease. Their preservation as important biomedical resources is critical. There is currently a need for populations of genetically-defined monkeys for biomedical investigation in the fields of transplant biology, stem cell biology, transgenics, gene therapy, infectious disease and vaccine development. In addition, the non-human primate model would be a highly valuable model for restoration of spermatogenesis in patients undergoing chemotherapy and radiation therapy. Isolation of spermatogonial stem cells before and autologous transplantation after treatment could be an efficient technique to reverse infertility. The long-term objective of the proposed research is to preserve and reconstitute genotypically unique non-human primates. Immediate objectives will be to develop a successful method to isolate and enrich non-human primate germ line precursor cells and to culture, cryopreserve, and transplant spermatogonial stem cells from genetically unique male macaques to immunodeficient mice and recipient male macaques. These objectives will be accomplished by investigation of the isolation and culture requirements of isolated macaque spermatogonia. We will then determine the specific characteristics of spermatogonial proliferation and differentiation of donor cells from rhesus and cynomolgus macaques transplanted to mouse recipients. We hypothesize that macaque sperm can be banked and then harvested from male mice or recipient macaques by semen collection and subsequently used in artificial insemination and IVF programs at the Regional Primate Research Centers in the US. This project represents a collaboration between Dr. Stuart Meyers, University California at Davis, and Dr. Ina Dobrinski, University of Pennsylvania. All experiments involving live macaques and in-vitro experiments involving selection, culture and freezing of macaque cells will be performed at UC Davis in the laboratory of Dr. Meyers. Experiments involving transplantation of macaque sperm cells into mouse testes will be performed at the University of Pennsylvania in the laboratory of Dr. Dobrinski and experiments involving germ cell transplantation into male macaques will be performed at UC Davis. We expect to expand this study into a fully-independent project.