Allogeneic Adipose-Derived Stem Cells Mitigate Acute Radiation Syndrome by the Rescue of Damaged Bone Marrow Cells from Apoptosis
العنوان: | Allogeneic Adipose-Derived Stem Cells Mitigate Acute Radiation Syndrome by the Rescue of Damaged Bone Marrow Cells from Apoptosis |
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المؤلفون: | Wen Hou, Yasamin Samadi, Michael W. Epperly, Katherine S. Yang, J. Peter Rubin, Asim Ejaz, Somaiah Chinnapaka, Joel S. Greenberger |
المصدر: | Stem Cells Translational Medicine, Vol 10, Iss 7, Pp 1095-1114 (2021) Stem Cells Translational Medicine |
بيانات النشر: | Oxford University Press (OUP), 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | 0301 basic medicine, Medicine (General), Adipose tissue, Apoptosis, Bone Marrow Cells, intraperitoneal injection, acute radiation syndrome, Mice, 03 medical and health sciences, R5-920, 0302 clinical medicine, Tissue Engineering and Regenerative Medicine, medicine, Animals, QH573-671, business.industry, Regeneration (biology), Hematopoietic Stem Cell Transplantation, Cell Biology, General Medicine, Total body irradiation, cytokines, hematopoiesis, Mice, Inbred C57BL, adipose stem cells, Haematopoiesis, 030104 developmental biology, medicine.anatomical_structure, Adipose Tissue, Cancer research, Tumor necrosis factor alpha, Bone marrow, Stem cell, Cytology, business, total body irradiation, 030217 neurology & neurosurgery, Developmental Biology |
الوصف: | 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, MIP1β, 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. |
تدمد: | 2157-6580 2157-6564 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6f804ee41c5ad94c73f384896b805583 https://doi.org/10.1002/sctm.20-0455 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....6f804ee41c5ad94c73f384896b805583 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 21576580 21576564 |
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