Takahiro Nishikawa1, Keiko Maeda2, Masanao Nakamura1, Takeshi Yamamura3, Tsunaki Sawada3, Yasuyuki Mizutani1, Takanori Ito1, Takuya Ishikawa1, Kazuhiro Furukawa1, Eizaburo Ohno1, Ryoji Miyahara1, Hiroki Kawashima3, Takashi Honda1, Masatoshi Ishigami1, Tokunori Yamamoto4,5, Seiji Matsumoto5,6, Yuji Hotta7, Mitsuhiro Fujishiro1. 1. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan. 2. Department of Endoscopy, Nagoya University Hospital, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan. kmaeda@med.nagoya-u.ac.jp. 3. Department of Endoscopy, Nagoya University Hospital, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan. 4. Laboratory for Clinical Application of Adipose-Derived Regenerative Cells, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan. 5. Clinical Research Support Center, Asahikawa Medical University Hospital, 2-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan. 6. Center for Advanced Research and Education, Asahikawa Medical University, 2-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan. 7. Department of Hospital Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 1-3 Tanabedori, Mizuho-ku, Nagoya, 467-8603, Japan.
Abstract
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.
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 colitismouse 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 colitismouse 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.
Authors: M F Pittenger; A M Mackay; S C Beck; R K Jaiswal; R Douglas; J D Mosca; M A Moorman; D W Simonetti; S Craig; D R Marshak Journal: Science Date: 1999-04-02 Impact factor: 47.728
Authors: Geoffrey M Forbes; Marian J Sturm; Rupert W Leong; Miles P Sparrow; Dev Segarajasingam; Adrian G Cummins; Michael Phillips; Richard P Herrmann Journal: Clin Gastroenterol Hepatol Date: 2013-07-19 Impact factor: 11.382
Authors: Siew C Ng; Hai Yun Shi; Nima Hamidi; Fox E Underwood; Whitney Tang; Eric I Benchimol; Remo Panaccione; Subrata Ghosh; Justin C Y Wu; Francis K L Chan; Joseph J Y Sung; Gilaad G Kaplan Journal: Lancet Date: 2017-10-16 Impact factor: 79.321
Authors: Chang-ho Ryan Choi; Ana Ignjatovic-Wilson; Alan Askari; Gui Han Lee; Janindra Warusavitarne; Morgan Moorghen; Siwan Thomas-Gibson; Brian P Saunders; Matthew D Rutter; Trevor A Graham; Ailsa L Hart Journal: Am J Gastroenterol Date: 2015-09-29 Impact factor: 10.864