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Allogeneic adipose-derived stem cells mitigate acute radiation syndrome by the rescue of damaged bone marrow cells from apoptosis.
Chinnapaka, Somaiah; Yang, Katherine S; Samadi, Yasamin; Epperly, Michael W; Hou, Wen; Greenberger, Joel S; Ejaz, Asim; Rubin, J Peter.
Afiliación
  • Chinnapaka S; Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Yang KS; Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Samadi Y; Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Epperly MW; Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
  • Hou W; Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
  • Greenberger JS; Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
  • Ejaz A; Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Rubin JP; Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Stem Cells Transl Med ; 10(7): 1095-1114, 2021 07.
Article en En | MEDLINE | ID: mdl-33724714
Acute radiation syndrome (ARS) is the radiation toxicity that can affect the hematopoietic, gastrointestinal, and nervous systems upon accidental radiation exposure within a short time. Currently, there are no effective and safe approaches to treat mass population exposure to ARS. Our study aimed to evaluate the therapeutic potential of allogeneic adipose-derived stem cells (ASCs) for total body irradiation (TBI)-induced ARS and understand the underlying mitigation mechanism. We employed 9.25 Gy TBI dose to C57BL/6 mice and studied the effect of allogeneic ASCs on mice survival and regeneration of the hematopoietic system. Our results indicate that intraperitoneal-injected ASCs migrated to the bone marrow, rescued hematopoiesis, and improved the survival of irradiated mice. Our transwell coculture results confirmed the migration of ASCs to irradiated bone marrow and rescue hematopoietic activity. Furthermore, contact coculture of ASCs improved the survival and hematopoiesis of irradiated bone marrow in vitro. Irradiation results in DNA damage, upregulation of inflammatory signals, and apoptosis in bone marrow cells, while coculture with ASCs reduces apoptosis via activation of DNA repair and the antioxidation system. Upon exposure to irradiated bone marrow cells, ASCs secrete prosurvival and hematopoietic factors, such as GM-CSF, MIP1α, MIP1ß, LIX, KC, 1P-10, Rantes, IL-17, MCSF, TNFα, Eotaxin, and IP-10, which reduces oxidative stress and rescues damaged bone marrow cells from apoptosis. Our findings suggest that allogeneic ASCs therapy is effective in mitigating TBI-induced ARS in mice and may be beneficial for clinical adaptation to treat TBI-induced toxicities. Further studies will help to advocate the scale-up and adaptation of allogeneic ASCs as the radiation countermeasure.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células de la Médula Ósea / Apoptosis / Trasplante de Células Madre Hematopoyéticas / Síndrome de Radiación Aguda Límite: Animals Idioma: En Revista: Stem Cells Transl Med Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células de la Médula Ósea / Apoptosis / Trasplante de Células Madre Hematopoyéticas / Síndrome de Radiación Aguda Límite: Animals Idioma: En Revista: Stem Cells Transl Med Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido