2. Academic Validation
  3. Umbilical cord/placenta-derived mesenchymal stem cells inhibit fibrogenic activation in human intestinal myofibroblasts via inhibition of myocardin-related transcription factor A

Umbilical cord/placenta-derived mesenchymal stem cells inhibit fibrogenic activation in human intestinal myofibroblasts via inhibition of myocardin-related transcription factor A

  • Stem Cell Res Ther. 2019 Sep 23;10(1):291. doi: 10.1186/s13287-019-1385-8.
Yoon Jeong Choi 1 2,  Jun Bon Koo 3,  Hee Yeon Kim 4,  Jin Won Seo 4,  Eun Jeong Lee 4,  Woo Ram Kim 5,  Joo Young Cho 1,  Ki Baik Hahm 1,  Sung Pyo Hong 1,  Duk Hwan Kim 6,  Jun-Hwan Yoo 7 8
Affiliations

Affiliations

  • 1 Digestive Disease Center, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam, 463-712, South Korea.
  • 2 Institute of Basic Medical Sciences, School of Medicine, CHA University, Seongnam, South Korea.
  • 3 Clinical Research Center, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
  • 4 CHA Biotech, Co. Ltd., Seongnam, South Korea.
  • 5 Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
  • 6 Digestive Disease Center, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam, 463-712, South Korea. [email protected].
  • 7 Digestive Disease Center, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam, 463-712, South Korea. [email protected].
  • 8 Institute of Basic Medical Sciences, School of Medicine, CHA University, Seongnam, South Korea. [email protected].
PMID: 31547873 DOI: 10.1186/s13287-019-1385-8
Abstract

Background: The lack of anti-fibrotic agents targeting intestinal fibrosis is a large unmet need in inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. Previous studies have found that perinatal tissue (umbilical cord, UC; placenta, PL)-derived mesenchymal stem cells (MSCs) reduce fibrosis in several organs. However, their effects on human intestinal fibrosis are poorly understood. This study investigated the anti-fibrogenic properties and mechanisms of MSCs derived from UC and PL (UC/PL-MSCs) on human primary intestinal myofibroblasts (HIMFs).

Methods: The HIMFs were treated with TGF-β1 and co-cultured with UC/PL-MSCs. We used a small molecular inhibitor CCG-100602 to examine whether serum response factor (SRF) and its transcriptional cofactor myocardin-related transcription factor A (MRTF-A) are involved in TGF-β1-induced fibrogenic activation in HIMFs. The anti-fibrogenic mechanism of UC/PL-MSCs on HIMFs was analyzed by detecting the expression of RhoA, MRTF-A, and SRF in HIMFs.

Results: UC/PL-MSCs reduced TGF-β1-induced procollagen1A1, fibronectin, and α-smooth muscle actin expression in HIMFs. This anti-fibrogenic effect was more apparent in the UC-MSCs. TGF-β1 stimulation increased the expressions of RhoA, MRTF-A, and SRF in the HIMFs. TGF-β1 induced the synthesis of procollagen1A1, fibronectin, and α-smooth muscle actin through a MRTF-A/SRF-dependent mechanism. Co-culture with the UC/PL-MSCs downregulated fibrogenesis by inhibition of RhoA, MRTF-A, and SRF expression.

Conclusions: UC/PL-MSCs suppress TGF-β1-induced fibrogenic activation in HIMFs by blocking the Rho/MRTF/SRF pathway and could be considered as a novel candidate for stem cell-based therapy of intestinal fibrosis.

Keywords

Intestinal fibrosis; Mesenchymal stem cells; Myofibroblasts; Placenta; Umbilical cord.

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