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Human Umbilical Cord Mesenchymal Stem Cell Delievers Exogenous miR-543 Via Exosome to Attenuate Radiation Induced Lung Injury
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A2964 - Human Umbilical Cord Mesenchymal Stem Cell Delievers Exogenous miR-543 Via Exosome to Attenuate Radiation Induced Lung Injury
Author Block: S. Xu1, C. Liu1, Y. Ma1, H. Ji2; 1Institute of Lung and Molecular Therapy, Xinxiang, China, 2University of Texas Health Center at Tyler, Tyler, TX, United States.
Radiation-induced lung injury (RILI) is a common complication in radiotherapy of thoracic tumors, which is a limiting factor for improving the radiation dose of the target area, affecting the quality of life of patients. There are currently no effective treatments clinically. MicroRNAs (miRNAs) act as important posttranscriptional regulators of diverse networks including inflammatory and fibrotic response networks. To find out the mechanism of miRNA-modified hUCMSC-exosomes therapy on RILI, in this study, we performed miRNA microarray to identify differentially expressed miRNAs in serum between normal C57BL/6 mice and C57BL/6 mice following whole-thorax lung irradiation. The profiles showed miR-543 was significantly down-regulated in RILI mice. We further over-expressed miR-543 in human umbilical cord mesenchymal stem cell (hUCMSC) and delivered the miR-543-expressing hUCMSC-exosomes into RILI mice through the tail veins. Compared to control hUCMSC-exosomes, hUCMSC-exosomes over-expressing miR-543 more effectively suppressed the TLR4/p65 signaling pathway via directly targeting 3’UTR of TLR4 and further alleviated inflammation response via reducing the expression of the pro-inflammatory cytokines IL-1β, IL-6 ,IL-8 and tumor necrosis factor-α (TNF-α) and increasing levels of the anti-inflammatory cytokine IL-10 in the serum and BALF of RILI mice. IHC examination showed hUCMSC-exosomes over-expressing miR-543 also down-regulated more transforming growth factor-β1, α -smooth muscle actin and type 1 collagen levels in irradiated lung tissues. The data above suggested miRNA-modified hUCMSC-exosomes can improve the ability of anti-inflammation of MSCs -exosome therapy without carcinogenic potential of MSCs and may be a safe, effective cell-free therapeutic strategy for RILI.
Author Block: S. Xu1, C. Liu1, Y. Ma1, H. Ji2; 1Institute of Lung and Molecular Therapy, Xinxiang, China, 2University of Texas Health Center at Tyler, Tyler, TX, United States.
Radiation-induced lung injury (RILI) is a common complication in radiotherapy of thoracic tumors, which is a limiting factor for improving the radiation dose of the target area, affecting the quality of life of patients. There are currently no effective treatments clinically. MicroRNAs (miRNAs) act as important posttranscriptional regulators of diverse networks including inflammatory and fibrotic response networks. To find out the mechanism of miRNA-modified hUCMSC-exosomes therapy on RILI, in this study, we performed miRNA microarray to identify differentially expressed miRNAs in serum between normal C57BL/6 mice and C57BL/6 mice following whole-thorax lung irradiation. The profiles showed miR-543 was significantly down-regulated in RILI mice. We further over-expressed miR-543 in human umbilical cord mesenchymal stem cell (hUCMSC) and delivered the miR-543-expressing hUCMSC-exosomes into RILI mice through the tail veins. Compared to control hUCMSC-exosomes, hUCMSC-exosomes over-expressing miR-543 more effectively suppressed the TLR4/p65 signaling pathway via directly targeting 3’UTR of TLR4 and further alleviated inflammation response via reducing the expression of the pro-inflammatory cytokines IL-1β, IL-6 ,IL-8 and tumor necrosis factor-α (TNF-α) and increasing levels of the anti-inflammatory cytokine IL-10 in the serum and BALF of RILI mice. IHC examination showed hUCMSC-exosomes over-expressing miR-543 also down-regulated more transforming growth factor-β1, α -smooth muscle actin and type 1 collagen levels in irradiated lung tissues. The data above suggested miRNA-modified hUCMSC-exosomes can improve the ability of anti-inflammation of MSCs -exosome therapy without carcinogenic potential of MSCs and may be a safe, effective cell-free therapeutic strategy for RILI.
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