Efficiency of ex vivo expansion in the treatment of bone marrow aplasia in a non-human primate model

Abstract

We have previously showed that non-human primate (NHP) (macaca fascicularis) mononucleated cells (MNC) can be expanded in different culture conditions, allowing the ex vivo expansion of either immature cells or mature cells. Thus, we tested the efficiency of expanded cells, either mature or immature, in treating the bone marrow aplasia resulting from total body irradiation (TBI). Three animals were irradiated at 8 Gy TBI, and were engrafted with the product of ex vivo expansion of 3 × 107 MNC/kg of body weight. Expansions were made during either 7 days or 14 days. 7-day expansion gave mainly immature cells that were injected on day 1 post-irradiation, while 14-day expansion gave rise mainly to mature cells, that were injected on day 8 post-irradiation. All cells were stained with CFSE before injection, in order to follow their kinetics in the peripheral blood. Results showed that a 7-day ex vivo expansion of 3 × 107 MNC/kg was sufficient to overcome the bone marrow aplasia with respect to neutrophils and platelets, with an outcome on day 23 post-irradiation. By contrast, a 14-day expansion injected on day 8 post-irradiation was not efficient in treating the aplasia, although circulating expanded cells were observed, as shown by CFSE staining. Overall, although the number of animals used in this preliminary study was limited, these results indicate the efficacy of ex vivo expansion of bone marrow MNC during 7 days in the treatment of radiation-induced bone marrow aplasia.