MESENCHYMAL STROMAL CELLS PROTECT FROM ACUTE RADIATION SYNDROMES: INSIGHTS INTO POSSIBLE MECHANISMS
https://doi.org/10.25016/2541-7487-2015-0-1-58-70
Abstract
Successful treatment of acute radiation syndromes relies on immediate supportive care. In patients with limited hematopoietic recovery potential, hematopoietic stem cell (HSC) transplantation is the only curative treatment option. We propose MSC treatment as an alternative treatment for severely radiation-affected individuals. In vitro differentiation of human MSC (hMSC) into progenitors for hematopoietic and endothelial cells revealed that MSC changed their morphology and gene expression profile, suggesting that investigated cells possess hematapoietic capacity in vitro. Mouse mesenchymal stromal cells (mMSCs) were expanded from bone marrow, retrovirally labeled with eGFP (bulk cultures) and cloned. Lethally irradiated recipients were i.v. transplanted with bulk or clonal mMSCs. We found a long-term survival of recipients with fast hematopoietic recovery after the transplantation of MSCs exclusively without support by HSCs. Quantitative PCR based chimerism analysis detected eGFP-positive donor cells in peripheral blood immediately after injection and in lungs within 24 hours. However, no donor cells in any investigated tissue remained long-term. Despite the rapidly disappearing donor cells, microarray and quantitative RT-PCR gene expression analysis in the bone marrow of MSC-transplanted animals displayed enhanced regenerative features characterized by decreased proinflammatory, ECM formation and adhesion properties and boosted anti-inflammation, detoxification, cell cycle and anti-oxidative stress control as compared to HSC transplanted animals. We could show that injection of MSC-derived microvesicles resulted in a similar protection as MSC transplantation. Our results suggest that MSCs, their release of trophic factors and their HSC-niche modulating activity rescue endogenous hematopoiesis thereby serving as fast and effective first-line treatment to combat radiation-induced hematopoietic failure.
Keywords
radiation,
radiobiology,
acute radiation sickness,
bone marrow,
hematopoietic stem cells,
mesenchymal stromal cells,
hematopoiesis,
irradiation
Supporting agencies: Federal Ministry of Education and Research, Germany, grant number 13N8904; “Deutsche José Carreras Leukämie-Stiftung e.V.”, grant number DJCLS R 12/30
About the Author
C. Lange
University Hospital Hamburg-Eppendorf
Germany
Germany
PhD, Clinic for Stem Cell Transplantation, Dept. Cell and Gene Therapy, University Hospital Hamburg–Eppendorf (Germany, 20246, Hamburg, Martini str., 52)
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Review
For citations:
Lange C. MESENCHYMAL STROMAL CELLS PROTECT FROM ACUTE RADIATION SYNDROMES: INSIGHTS INTO POSSIBLE MECHANISMS. Medicо-Biological and Socio-Psychological Problems of Safety in Emergency Situations. 2015;(1):58-70. (In Russ.) https://doi.org/10.25016/2541-7487-2015-0-1-58-70
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