Efficacy and mechanisms underlying the effects of allogeneic umbilical cord mesenchymal stem cell transplantation on acute radiation injury in tree shrews

• Published in: Cytotechnology (Dordrecht) 2018-10, Vol.70 (5), p.1447-1468
• Main Authors: Guo, De-Bin, Zhu, Xiang-Qing, Li, Qing-Qing, Liu, Gao-Mi-Yang, Ruan, Guang-Ping, Pang, Rong-Qing, Chen, Yu-Hao, Wang, Qiang, Wang, Jin-Xiang, Liu, Ju-Fen, Chen, Qiang, Pan, Xing-Hua
• Format: Article
• Language: English
• Subjects: Apoptosis; Biochemistry; Biomedicine; Biotechnology; Blood vessels; Bone marrow; Bone marrow transplantation; Bone morphogenetic protein 7; Chemistry; Chemistry and Materials Science; Cytokines; DNA microarrays; Experiments; Fibrosis; Flow cytometry; Gene expression; Growth factors; Hemopoiesis; Histocompatibility antigen HLA; Histology; Immunohistochemistry; Immunomodulation; Inflammation; Insulin-like growth factor-binding protein 2; Insulin-like growth factor-binding protein 4; Interleukin 1 receptor antagonist; Interleukin 1 receptors; Interleukin 10; Interleukin 13; Interleukin 2; Interleukin 8; Interleukins; Kidneys; Liver; Mesenchymal stem cells; Mesenchyme; Neurotrophin 4; Platelet-derived growth factor; Platelet-derived growth factor BB; Protein arrays; Radiation; Serum levels; Soricidae; Spleen; Stem cell transplantation; Stem cells; Survival analysis; Thymus; Tissue inhibitor of metalloproteinase 2; Transforming growth factor-b1; Tumor necrosis factor-α; Umbilical cord; Vascular endothelial growth factor receptors; Vectors (Biology); γ-Interferon
• ISSN: 0920-9069; 1573-0778
• DOI: 10.1007/s10616-018-0239-z

Umbilical cord mesenchymal stem cells (UC-MSCs) exert strong immunomodulatory effects and can repair organs. However, their roles in radiation injury remain unclear. We show that in tree shrews with acute radiation injury, injected UC-MSCs significantly improved survival rates, reduced lung inflammation and apoptosis, prevented pulmonary fibrotic processes, recovered hematopoiesis, and increased blood counts. A protein microarray analysis showed that serum levels of the anti-inflammatory cytokines IL-10 and IL-13 and the growth factors BMP-5, BMP-7, HGF, insulin, NT-4, VEGFR3, and SCF were significantly higher, while those of the inflammatory cytokines IL-2, TIMP-2, TNF-α, IFN-γ, IL-1ra, and IL-8 and the fibrosis-related factors PDGF-BB, PDGF-AA, TGF-β1, IGFBP-2, and IGFBP-4 were significantly lower in UC-MSC-injected animals. A transcriptome analysis of PBMCs showed that the mRNA expression of C1q was upregulated, while that of HLA-DP was downregulated after UC-MSC injection. These results confirm the immunohistochemistry results. eGFP-labeled UC-MSCs were traced in vivo and found in the heart, liver, spleen, lungs, kidneys, thymus, small intestine and bone marrow. Our findings suggest that UC-MSC transplantation may be a novel therapeutic approach for treating acute radiation injury.