Safe and efficient methods of autologous hematopoietic stem cell transplantation for biomedical research in cynomolgus monkeys.
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/microl. 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.
Ageyama
Naohide
N
Corporation for Production and Research of Laboratory Primates, lbaraki, Japan.
Hanazono
Yutaka
Y
Shibata
Hiroaki
H
Ohto
Keiko
K
Ono
Fumiko
F
Nagashima
Takeyuki
T
Ueda
Yasuji
Y
Donahue
Robert E
RE
Hasegawa
Mamoru
M
Ozawa
Keiya
K
Yoshikawa
Yasuhiro
Y
Terao
Keiji
K
D000818:Animals; D035843:Biomedical Research; D001772:Blood Cell Count / Q000662:veterinary; D001853:Bone Marrow; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000662:veterinary*; D008252:Macaca fascicularis; D008297:Male; D011182:Postoperative Care / Q000662:veterinary*; D011183:Postoperative Complications / Q000662:veterinary; D014182:Transplantation, Autologous / Q000379:methods*; D014916:Whole-Body Irradiation / Q000662:veterinary