Short term and prolonged effects of irradiation on human mesenchymal stem cells

Abstract

Background: Mesenchymal stem cells (MSCs) are important component of the bone marrow microenvironment and are progenitors of mesenchymal tissues. The effect of therapeutic irradiation to MSCs remains unexplored. Materials and Methods: MSCs were derived from healthy donors. Effects of irradiation with single dose (dosage ranges 2, 4, 6, 8, 12 Gy) on human MSCs were investigated. Post-irradiation cell proliferation was assessed by XTT assay and cell counting. Osteogenic and adipogenic differentiation function were evaluated after irradiation. ALP activity and calcium deposition in irradiated MSCs were quantified following osteogenic induction. Results: Irradiation inhibited proliferation of human MSCs up to 2 weeks post-irradiation but thereafter, survival cells regained normal proliferation rate back to the control level. ALP activity and calcium deposition were both reduced in a dose-dependant fashion. Maximum reduction (16% of control ALP activity and 9% of control calcium level) was noted in MSCs under 12 Gy irradiation. Adipocyte percentage was reduced by 50% in cultures that received irradiation >4 Gy. Attempts to protect the irradiated cells with 1 μM all-trans retinoic acid showed no protective effect on MSCs proliferation and differentiation. Conclusion: Irradiation damaged the capacity of human MSCs proliferation and differentiation. However, full recovery of growth and renewal ability was observed in surviving MSCs after 2 weeks.