4.5 Article

Hematopoietic recovery of acute radiation syndrome by human superoxide dismutase-expressing umbilical cord mesenchymal stromal cells

Journal

CYTOTHERAPY
Volume 17, Issue 4, Pages 403-417

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.jcyt.2014.11.011

Keywords

acute radiation syndrome; apoptosis; hematopoietic failure; stem cell; superoxide dismutase; umbilical cord mesenchymal stromal cells

Funding

  1. Shenzhen Research and Development grants [ZD201111080130A, CXY201107010176A, JSGG20130917151830203]
  2. California Institute of Regenerative Medicine (CIRM) [RT2-01942]
  3. National Institutes of Health [1R43 CA103553-01]
  4. Department of Defense [W81XWH-04-1-0597]
  5. Jilin International Collaboration Grant [20120720]
  6. NSFC [81272294]
  7. NATIONAL CANCER INSTITUTE [R43CA103553] Funding Source: NIH RePORTER

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Background aims. Acute radiation syndrome (ARS) leads to pancytopenia and multi-organ failure. Transplantation of hematopoietic stem cells provides a curative option for radiation-induced aplasia, but this therapy is limited by donor availability. Methods. We examined an alternative therapeutic approach to ARS with the use of human extracellular superoxide dismutase (ECSOD)-modified umbilical cord mesenchymal stromal cells (UCMSCs). This treatment combines the unique regenerative role of UCMSCs with the anti-oxidative activity of ECSOD. Results. We demonstrated that systemically administered ECSOD-UCMSCs are able to protect mice from sub-lethal doses of radiation and improve survival by promoting multilineage hematopoietic recovery. The therapeutic effect of this treatment is related to the decrease in radiation-induced O-2(-) and apoptosis. Conclusions. Our data highlight the clinical potential of this two-pronged approach to the treatment of ARS, thereby serving as a rapid and effective first-line strategy to combat the hematopoietic failure resulting from a radiation accident, nuclear terrorism and other radiologic emergencies.

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