Safe and Efficient Methods of Autologous Hematopoietic Stem Cell Transplantation for Biomedical Research in Cynomolgus Monkeys
Abstract:We have established safe and efficient methods for autologous hematopoietic stem cell (HSC) transplantation in cynomolgus monkeys (Macaca fascicularis) that include regimens of supportive care to ensure survival during hematopoietic reconstitution following otherwise lethal total body irradiation. Eleven young adult cynomolgus monkeys were studied. Bone marrow was aspirated from the ilium and/or tuber ischiae after administration of recombinant human stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF). Using the immunomagnetic selection method, CD34+ cells were then isolated (90 to 95% pure) as a fraction containing HSCs. Just prior to transplantation, the animals received myeloablative total body irradiation—500 to 550 cGy daily for two days. The monkeys re-infused with CD34+ cells developed moderate to severe myelosuppression, with some animals requiring intravenous hyperalimentation, antibiotic administration, and blood transfusion. Hematopoiesis was restored in all animals after transplantation. It took 12 days, on average, until the peripheral white blood cell count reached more than 1,000 cells/l. Up to two years after transplantation, signs of radiation-induced pneumonitis or other radiation-related disorders were not evident at the aforementioned dose of irradiation. This transplantation model will be useful for testing new approaches using HSCs for therapy of many diseases and will offer unique insights into the biology of these cells.
Document Type: Research Article
Affiliations: 1: Corporation for Production and Research of Laboratory Primates, Ibaraki 305-0843, Japan; Tsukuba Primate Center, National Institute of Infectious Diseases, Ibaraki 305-0843, Japan 2: Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical School, Tochigi 329-0498, Japan 3: Tsukuba Primate Center, National Institute of Infectious Diseases, Ibaraki 305-0843, Japan 4: Corporation for Production and Research of Laboratory Primates, Ibaraki 305-0843, Japan 5: DNAVEC Research Inc., Ibaraki 305-0856, Japan 6: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 7: Department of Biomedical Science, Graduate School of Agriculture and Life Science, University of Tokyo, Tokyo 113-8657, Japan
Publication date: October 1, 2002
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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