TY - JOUR
T1 - Filtrated Adipose Tissue-Derived Mesenchymal Stem Cell Lysate Ameliorates Experimental Acute Colitis in Mice
AU - Nishikawa, Takahiro
AU - Maeda, Keiko
AU - Nakamura, Masanao
AU - Yamamura, Takeshi
AU - Sawada, Tsunaki
AU - Mizutani, Yasuyuki
AU - Ito, Takanori
AU - Ishikawa, Takuya
AU - Furukawa, Kazuhiro
AU - Ohno, Eizaburo
AU - Miyahara, Ryoji
AU - Kawashima, Hiroki
AU - Honda, Takashi
AU - Ishigami, Masatoshi
AU - Yamamoto, Tokunori
AU - Matsumoto, Seiji
AU - Hotta, Yuji
AU - Fujishiro, Mitsuhiro
N1 - Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Background: Inflammatory bowel disease (IBD) is a chronic, persistent, and intractable enteritis; however, an effective treatment strategy is yet to be established. Mesenchymal stem cells (MSCs) and their paracrine factors exhibit anti-inflammatory actions and have been proposed as a new therapeutic candidate for IBD treatment, although the efficacy of MSC lysate on enteritis is unclear. Aims: Here, we examined the efficacy and appropriate regimen of filtrated murine adipose-derived mesenchymal stem cell lysate (FADSTL) in an acute colitis mouse model as a novel cell-free MSC therapy. Methods: To confirm the clinical effects of FADSTL, survival rate, body weight, and disease activity index (DAI) were investigated in the DSS-induced colitis mouse model. Further, differences in efficacy with dosing frequency were assessed to optimize the proper regimen. Colon length, histological findings, gene expression of inflammatory mediators and tight junction proteins in colon tissues, and anti-apoptotic effects were also compared in 3-day continuous FADSTL administration and PBS groups. Results: Three-day continuous FADSTL administration significantly improved weight loss and DAI score compared to those in the PBS-treated group, whereas the effect was not observed with single administration. Additionally, colon shortening and histological inflammation were suppressed in the FADSTL-treated group. Further, this treatment decreased gene expression of inflammatory mediators, maintained expression of tight junction proteins in the colon, and showed anti-apoptotic effects. Conclusions: FADSTL effects were dependent on its administration frequency, suggesting the requirement of continuous FADSTL administration. FADSTL improved colitis by maintaining the intestinal barrier function through its anti-inflammatory and anti-apoptotic actions.
AB - Background: Inflammatory bowel disease (IBD) is a chronic, persistent, and intractable enteritis; however, an effective treatment strategy is yet to be established. Mesenchymal stem cells (MSCs) and their paracrine factors exhibit anti-inflammatory actions and have been proposed as a new therapeutic candidate for IBD treatment, although the efficacy of MSC lysate on enteritis is unclear. Aims: Here, we examined the efficacy and appropriate regimen of filtrated murine adipose-derived mesenchymal stem cell lysate (FADSTL) in an acute colitis mouse model as a novel cell-free MSC therapy. Methods: To confirm the clinical effects of FADSTL, survival rate, body weight, and disease activity index (DAI) were investigated in the DSS-induced colitis mouse model. Further, differences in efficacy with dosing frequency were assessed to optimize the proper regimen. Colon length, histological findings, gene expression of inflammatory mediators and tight junction proteins in colon tissues, and anti-apoptotic effects were also compared in 3-day continuous FADSTL administration and PBS groups. Results: Three-day continuous FADSTL administration significantly improved weight loss and DAI score compared to those in the PBS-treated group, whereas the effect was not observed with single administration. Additionally, colon shortening and histological inflammation were suppressed in the FADSTL-treated group. Further, this treatment decreased gene expression of inflammatory mediators, maintained expression of tight junction proteins in the colon, and showed anti-apoptotic effects. Conclusions: FADSTL effects were dependent on its administration frequency, suggesting the requirement of continuous FADSTL administration. FADSTL improved colitis by maintaining the intestinal barrier function through its anti-inflammatory and anti-apoptotic actions.
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U2 - 10.1007/s10620-020-06359-3
DO - 10.1007/s10620-020-06359-3
M3 - Article
C2 - 32488819
AN - SCOPUS:85085883836
JO - American Journal of Digestive Diseases
JF - American Journal of Digestive Diseases
SN - 0002-9211
ER -