Mesenchymal Stem Cells show high radioprotective activity in vivo

Résumé 0

Radiotherapy puts bones at risk of developing osteonecrosis. Irradiation has an impact on the viability as well as the differentiation capacity of mesenchymal stem cells (MSC), which play a pivotal role in bone regeneration. To investigate the effect of irradiation on MSC, human bone-derived MSC were irradiated in vitro. With increasing doses the cells’ self-renewal capabilities were greatly reduced. Notably however, mitotically stalled cells were still capable of differentiating into osteoblasts and preadipocytes. Next the pigs mandibles were subjected to fractionized radiation of 2x9 Gy within one week. This treatment mimicks that of a standardized clinical treatment regimen of a head and neck cancer patient (30x2 Gy). Fractures, which had been deliberately generated and subsequently irradiated showed retarded osseous healing. When isolating MSC from irradiated sites at different time points post irradiation, no significant changes in comparison to cells derived from un-irradiated specimens regarding proliferation capacity and osteogenic differentiation potential became apparent. Therefore, pig mandibles were irradiated with 9 and 18 Gy in vivo, and MSC were isolated immediately afterwards. No significant differences between the untreated and 9 Gy -irradiated bone with respect to proliferation and osteogenic differentiation were unveiled. Yet, cells isolated from 18 Gy irradiated specimens exhibited a reduced osteogenic differentiation capacity, and during the first two weeks proliferation rates were greatly diminished. Thereafter, cells recovered and showed normal proliferation behaviour. These findings imply that MSC can cope with irradiation up to high doses in vivo, and could be implemented in future therapeutic concepts to protect from osteonecrosis.

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