RETRACTED ARTICLE: Pre-activation of mesenchymal stem cells with TNF-α, IL-1β and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury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

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Main Authors: Hao Chen, Xiao-Hui Min, Qi-Yi Wang, Felix W. Leung, Liu Shi, Yu Zhou, Tao Yu, Chuan-Ming Wang, Geng An, Wei-Hong Sha, Qi-Kui Chen
Format: Article
Language:English
Published: Nature Portfolio 2015-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/srep08718
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author Hao Chen
Xiao-Hui Min
Qi-Yi Wang
Felix W. Leung
Liu Shi
Yu Zhou
Tao Yu
Chuan-Ming Wang
Geng An
Wei-Hong Sha
Qi-Kui Chen
author_facet Hao Chen
Xiao-Hui Min
Qi-Yi Wang
Felix W. Leung
Liu Shi
Yu Zhou
Tao Yu
Chuan-Ming Wang
Geng An
Wei-Hong Sha
Qi-Kui Chen
author_sort Hao Chen
collection DOAJ
description 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 (MSCIEC-6(IR)) and investigated the evidence and mechanism for the differential effects of MSC-CMIEC-6(IR) and non-activated MSC-CM on radiation-induced intestinal injury (RIII). Systemic infusion of MSC-CMIEC-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 MSCIEC-6(IR) is related to a higher secretion of regenerative, immunomodulatory and trafficking molecules, including the pivotal factor IGF-1, induced by TNF-α, IL-1β and nitric oxide partially via a heme oxygenase-1 dependent mechanism. Together, our findings suggest that pre-activation of MSCs with TNF-α, IL-1β 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.
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spelling doaj-art-b7e67251629944de8a362a4184ec17a72025-08-20T02:16:34ZengNature PortfolioScientific Reports2045-23222015-03-015111410.1038/srep08718RETRACTED ARTICLE: Pre-activation of mesenchymal stem cells with TNF-α, IL-1β and nitric oxide enhances its paracrine effects on radiation-induced intestinal injuryHao Chen0Xiao-Hui Min1Qi-Yi Wang2Felix W. Leung3Liu Shi4Yu Zhou5Tao Yu6Chuan-Ming Wang7Geng An8Wei-Hong Sha9Qi-Kui Chen10Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Gastroenterology, Guangdong General Hospital and Guangdong Academy of Medical SciencesDivision of Gastroenterology, David Geffen School of Medicine at University of CaliforniaDepartment of Gastroenterology, Ganzhou People's HospitalDepartment of Gastroenterology, Affiliated Hospital of Guangdong Medical CollegeDepartment of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Neurology, Shenzhen Sixth People's HospitalDepartment of Reproductive Medicine Center, The Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Gastroenterology, Guangdong General Hospital and Guangdong Academy of Medical SciencesDepartment of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityAbstract 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 (MSCIEC-6(IR)) and investigated the evidence and mechanism for the differential effects of MSC-CMIEC-6(IR) and non-activated MSC-CM on radiation-induced intestinal injury (RIII). Systemic infusion of MSC-CMIEC-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 MSCIEC-6(IR) is related to a higher secretion of regenerative, immunomodulatory and trafficking molecules, including the pivotal factor IGF-1, induced by TNF-α, IL-1β and nitric oxide partially via a heme oxygenase-1 dependent mechanism. Together, our findings suggest that pre-activation of MSCs with TNF-α, IL-1β 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.https://doi.org/10.1038/srep08718
spellingShingle Hao Chen
Xiao-Hui Min
Qi-Yi Wang
Felix W. Leung
Liu Shi
Yu Zhou
Tao Yu
Chuan-Ming Wang
Geng An
Wei-Hong Sha
Qi-Kui Chen
RETRACTED ARTICLE: Pre-activation of mesenchymal stem cells with TNF-α, IL-1β and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury
Scientific Reports
title RETRACTED ARTICLE: Pre-activation of mesenchymal stem cells with TNF-α, IL-1β and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury
title_full RETRACTED ARTICLE: Pre-activation of mesenchymal stem cells with TNF-α, IL-1β and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury
title_fullStr RETRACTED ARTICLE: Pre-activation of mesenchymal stem cells with TNF-α, IL-1β and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury
title_full_unstemmed RETRACTED ARTICLE: Pre-activation of mesenchymal stem cells with TNF-α, IL-1β and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury
title_short RETRACTED ARTICLE: Pre-activation of mesenchymal stem cells with TNF-α, IL-1β and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury
title_sort retracted article pre activation of mesenchymal stem cells with tnf α il 1β and nitric oxide enhances its paracrine effects on radiation induced intestinal injury
url https://doi.org/10.1038/srep08718
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