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Pre-activation of mesenchymal stem cells with TNF-?, IL-1? and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury.

ABSTRACT: Conditioned medium from mesenchymal stem cells (MSC-CM) may represent a promising alternative to MSCs transplantation, however, the low concentrations of growth factors in non-activated MSC-CM hamper its clinical application. Recent data indicated that the paracrine potential of MSCs could be enhanced by inflammatory factors. Herein, we pre-activated bone-marrow-derived MSCs under radiation-induced inflammatory condition (MSC(IEC-6(IR))) and investigated the evidence and mechanism for the differential effects of MSC-CM(IEC-6(IR)) and non-activated MSC-CM on radiation-induced intestinal injury (RIII). Systemic infusion of MSC-CM(IEC-6(IR)), but not non-activated MSC-CM, dramatically improved intestinal damage and survival of irradiated rats. Such benefits may involve the modulation of epithelial regeneration and inflammation, as indicated by the regeneration of intestinal epithelial/stem cells, the regulation of the pro-/anti-inflammatory cytokine balance. The mechanism for the superior paracrine efficacy of MSC(IEC-6(IR)) is related to a higher secretion of regenerative, immunomodulatory and trafficking molecules, including the pivotal factor IGF-1, induced by TNF-?, IL-1? and nitric oxide partially via a heme oxygenase-1 dependent mechanism. Together, our findings suggest that pre-activation of MSCs with TNF-?, IL-1? and nitric oxide enhances its paracine effects on RIII via a heme oxygenase-1 dependent mechanism, which may help us to maximize the paracrine potential of MSCs.

SUBMITTER: Chen H

PROVIDER: S-EPMC4346809 | biostudies-other | 2015 Mar

REPOSITORIES: biostudies-other

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Pre-activation of mesenchymal stem cells with TNF-α, IL-1β and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury.

Chen Hao H Min Xiao-Hui XH Wang Qi-Yi QY Leung Felix W FW Shi Liu L Zhou Yu Y Yu Tao T Wang Chuan-Ming CM An Geng G Sha Wei-Hong WH Chen Qi-Kui QK

Scientific reports 20150303

Conditioned medium from mesenchymal stem cells (MSC-CM) may represent a promising alternative to MSCs transplantation, however, the low concentrations of growth factors in non-activated MSC-CM hamper its clinical application. Recent data indicated that the paracrine potential of MSCs could be enhanced by inflammatory factors. Herein, we pre-activated bone-marrow-derived MSCs under radiation-induced inflammatory condition (MSC(IEC-6(IR))) and investigated the evidence and mechanism for the differ ...[more]

PMID: 25732721

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Dataset Information

Pre-activation of mesenchymal stem cells with TNF-?, IL-1? and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury.

Publications

Pre-activation of mesenchymal stem cells with TNF-α, IL-1β and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury.

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