智发朝团队:胚胎干细胞源性间充质干细胞或可治疗结肠炎
  • 从人类胚胎干细胞获得表型均一的间充质干细胞(T-MSCs),静脉注射给小鼠可减轻急性和慢性DSS诱导结肠炎症状;
  • 静脉注射后,T-MSCs主要分布在肺、肝、脾;
  • 治疗组IGF-1水平升高,且IGF-1是在再生期升高,腹腔注射IGF-1受体抑制剂可抑制T-MSCs的抗炎活性;
  • 治疗组结肠上皮细胞的再生能力强于对照组,且IGF1R-PI3K-AKT通路上调;
  • T-MSCs移植有助于结肠细胞的完整性,促进外源性代谢;
  • 体外IGF-1刺激可促进结肠细胞和类器官的生长和增殖。
主编推荐语
爱的抉择
间充质干细胞(MSCs)由于具有免疫调节和营养功能,在治疗炎症性肠病(IBD)方面显示出良好的治疗潜力,但疗效受限于组织来源、供体条件、分离和扩张方法等影响。南方医科大学南方医院智发朝与团队在Theranostics发表文章,利用人类胚胎干细胞来源的间充质干细胞(T-MSCs)可改善小鼠的结肠炎症状,而且间充质干细胞的移植提高小鼠IGF-1水平,促进结肠上皮的修复和再生。研究提示,T-MSCs或是治疗IBD的潜在细胞来源。
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Theranostics [IF:8.579]

Embryonic stem cell-derived mesenchymal stem cells promote colon epithelial integrity and regeneration by elevating circulating IGF-1 in colitis mice

胚胎干细胞源性间充质干细胞通过提高循环IGF-1促进结肠炎小鼠的结肠上皮完整性和再生

10.7150/thno.47683

2020-10-30, Article

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Rationale: Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating inflammatory bowel disease (IBD) due to their immunomodulatory and trophic functions. However, their efficacy is influenced by tissue origin, donator condition, isolation, and expansion methods. Here, we generated phenotypically uniform MSCs from human embryonic stem cells (T-MSCs) and explored the molecular mechanisms involved in promoting mucosal integrity and regeneration in colitis mice.
Methods: T-MSCs were injected intravenously into mice with dextran sulfate sodium (DSS)-induced colitis, and the in vivo distribution and therapeutic efficacy were evaluated. We performed serum cytokine antibody microarrays to screen potentially effective proteins and examined the therapeutic effect of insulin-like growth factor-1 (IGF-1). Colon epithelial regeneration potential was evaluated, and RNA sequencing was employed to determine the underlying molecular mechanisms. Finally, in vitro IGF-1 stimulation was performed to assess its effect on cell functions and organoid growth.
Results: Intravenous administration of T-MSCs alleviated colitis in both acute and chronic DSS mouse models. Labeled T-MSCs were mainly distributed in the lungs, liver, and spleen after systemic infusion. The antibody array analysis of serum cytokines indicated that the IGF-1 level was increased in the treatment group, and serum ELISA further confirmed its elevation in the regeneration stage. Intraperitoneal injection of IGF-1 receptor inhibitors abrogated the anti-inflammatory activity of T-MSCs. The colonic epithelium of the treatment group showed greater regenerative potency than the controls and the IGF1R-PI3K-AKT pathway was up-regulated. RNA sequencing showed that T-MSC treatment contributed to colonic cell integrity and promoted xenobiotic metabolism. In vitro IGF-1 stimulation promoted the growth and proliferation of colon cells and organoids.
Conclusions: Intravenous infusion of T-MSCs alleviated colitis in mice by elevating the circulating IGF-1 level. Increased IGF-1 maintained the integrity of epithelial cells and contributed to their repair and regeneration. Our study has identified T- MSCs as a potential cell resource for IBD treatment.

First Authors:
Jun Xu

Correspondence Authors:
Fachao Zhi

All Authors:
Jun Xu,Xiaofang Wang,Jiaye Chen,Shengbo Chen,Zhijun Li,Hongbin Liu,Yang Bai,Fachao Zhi

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