Treating Total Body Irradiation with Allogeneic Adipose-derived Stem Cells

Review of "Allogeneic adipose‐derived stem cells mitigate acute radiation syndrome by the rescue of damaged bone marrow cells from apoptosis" from STEM CELLS Translational Medicine by Stuart P. Atkinson

The development of allogenic cell therapies that indirectly support the recovery of hematopoiesis represents an attractive alternative to hematopoietic stem cell transplantation as a treatment for acute radiation syndrome caused by total body irradiation [1, 2]. Adipose-derive stem cells (ASCs) can be easily isolated in large numbers; furthermore, these stem cells display low immunogenicity, exert anti‐inflammatory and immunosuppressive effects that support the regeneration of damaged tissues, the amelioration of radiation‐induced fibrosis [3], and the regeneration of the hematopoietic system following bone marrow damage [4, 5].

Given these encouraging studies, researchers led by Asim Ejaz and J. Peter Rubin (University of Pittsburgh Medical Center, Pittsburgh, PA, USA) recently explored the potential of allogeneic, cell culture-propagated ASCs as a therapeutic approach to acute radiation syndrome. In their recent STEM CELLS Translational Medicine study [6], Chinnapaka et al. now report that intraperitoneally injected allogeneic ASCs migrate to the irradiated mouse bone marrow and induce repair by secreting hematopoietic and pro-survival factors, thereby suggesting allogeneic ASCs as a potentially safe and effective means to inhibit acute radiation syndrome in populations exposed to irradiation.

The authors intraperitoneally administered allogeneic ASCs in mice that had previously been exposed to total body irradiation and demonstrated that injected cells migrated to the bone marrow to rescue hematopoiesis and improved overall survival to a level comparable to autologous ASCs. Subsequent in vitro studies using transwell cocultures confirmed that ASCs migrated through inserts towards irradiated bone marrow cells (but not unirradiated cells), where they rescued hematopoietic activity and improved survival. Additionally, contact coculture of ASCs also further improved the survival of irradiated bone marrow cells and supported hematopoiesis. At the mechanistic level, ASC coculture appeared to reduce apoptosis of irradiated bone marrow cells by enhancing DNA repair and boosting anti-oxidative activities thanks to the secretion and activity of a wide range of immunomodulatory, anti‐inflammatory, antioxidant, pro-survival, and pro-hematopoietic factors.

Overall, the authors provide robust evidence for the potential of allogeneic ASC therapy as an amenable means to mitigate acute radiation syndrome following total body irradiation. The authors hope to now take the next steps towards developing allogeneic ASC therapy as a clinical reality for human patients.

For more on how allogeneic adipose-derived stem cells may represent a safe, amenable, and effective treatment strategy for human patients recovering from total body irradiation, stay tuned to the Stem Cells Portal!

References

1. Wills C, Cherian S, Yousef J, et al., Total body irradiation: a practical review. Applied Radiation Oncology 2016;5:11-17.
2. Donnelly EH, Nemhauser JB, Smith JM, et al., Acute radiation syndrome: assessment and management. Southern Medical Journal 2010;103:541-6.
3. Ejaz A, Epperly MW, Hou W, et al., Adipose-Derived Stem Cell Therapy Ameliorates Ionizing Irradiation Fibrosis via Hepatocyte Growth Factor-Mediated Transforming Growth Factor-β Downregulation and Recruitment of Bone Marrow Cells. STEM CELLS 2019;37:791-802.
4. Cousin B, André M, Arnaud E, et al., Reconstitution of lethally irradiated mice by cells isolated from adipose tissue. Biochemical and Biophysical Research Communications 2003;301:1016-1022.
5. Corre J, Barreau C, Cousin B, et al., Human subcutaneous adipose cells support complete differentiation but not self-renewal of hematopoietic progenitors. Journal of Cellular Physiology 2006;208:282-288.
6. Chinnapaka S, Yang KS, Samadi Y, et al., Allogeneic adipose-derived stem cells mitigate acute radiation syndrome by the rescue of damaged bone marrow cells from apoptosis. STEM CELLS Translational Medicine 2021;10:1095-1114.