Application of autologous hematopoietic cell therapy to a nonhuman primate model of heterogeneous high-dose irradiation.
We developed a model of heterogeneous irradiation in a nonhuman primate to test the feasibility of autologous hematopoietic cell therapy for the treatment of radiation accident victims. Animals were irradiated either with 8 Gy to the body with the right arm shielded to obtain 3.4 Gy irradiation or with 10 Gy total body and 4.4 Gy to the arm. Bone marrow mononuclear cells were harvested either before irradiation or after irradiation from an underexposed area of the arm and were expanded in previously defined culture conditions. We showed that hematopoietic cells harvested after irradiation were able to expand and to engraft when reinjected 7 days after irradiation. Recovery was observed in all 8-Gy-irradiated animals, and evidence for a partial recovery was observed in 10-Gy-irradiated animals. However, in 10-Gy-irradiated animals, digestive disease was observed from day 16 and resulted in the death of two animals. Immunohistological examinations showed damage to the intestine, lungs, liver and kidneys and suggested radiation damage to endothelial cells. Overall, our results provide evidence that such an in vivo model of heterogeneous irradiation may be representative of accidental radiation exposures and may help to define the efficacy of therapeutic interventions such as autologous cell therapy in radiation accident victims.
Bertho
Jean-Marc
JM
Institut de Radioprotection et de Sûreté Nucléaire, Département de Radioprotection de l'Homme, Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle, Fontenay-aux-Roses, France. jean-marc.bertho@irsn.fr
Prat
Marie
M
Frick
Johanna
J
Demarquay
Christelle
C
Gaugler
Marie-Hélène
MH
Dudoignon
Nicolas
N
Clairand
Isabelle
I
Chapel
Alain
A
Gorin
Norbert-Claude
NC
Thierry
Dominique
D
Gourmelon
Patrick
P
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000528:radiation effects; D006410:Hematopoiesis / Q000528:radiation effects; D006413:Hematopoietic System / Q000166:cytology*; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008252:Macaca fascicularis; D008297:Male; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000628:therapy*; D014182:Transplantation, Autologous