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内镜下大鼠实验性结肠炎中间充质干细胞片的移植。

Endoscopic Transplantation of Mesenchymal Stem Cell Sheets in Experimental Colitis in Rats.

机构信息

Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

出版信息

Sci Rep. 2018 Jul 27;8(1):11314. doi: 10.1038/s41598-018-29617-x.

Abstract

Owing to the recent progress in regenerative medicine technology, clinical trials that harnessed the regeneration and immune modulation potentiality of stem cells for treating IBD have shown promising results. We investigated the feasibility and utility of intraluminal endoscopic transplantation of rat MSC sheets in murine models of experimental colitis for targeted delivery of stem cells to lesions. We isolated adipose-derived mesenchymal stem cells (AD-MSC) and bone marrow-derived mesenchymal stem cells (BM-MSC) from EGFP-transgenic rats and fabricated the cells in sheet forms using temperature-responsive culture dishes. The MSC sheets were endoscopically transplanted to the inflamed area in electrocoagulation and DNBS colitis model. The effect of the transplantation was verified using endoscopic scoring and histological analysis. In the electrocoagulation model, the AD-MSC group showed significantly decreased ulcer size in the transplanted regions. In the DNBS colitis model, the AD-MSC group showed decreased inflammation and colitis in the transplanted regions. Histologic analysis showed that the MSC sheets had successfully attached to the inflamed mucosa in both the electrocoagulation and DNBS colitis model. Our results show that endoscopic transplantation of MSC sheets could be a new effective mode of stem cell therapy for IBD treatment.

摘要

由于再生医学技术的最新进展,利用干细胞的再生和免疫调节潜力治疗 IBD 的临床试验已经显示出了有前景的结果。我们研究了腔内内镜移植大鼠 MSC 片在实验性结肠炎小鼠模型中用于将干细胞靶向递送至病变部位的可行性和实用性。我们从 EGFP 转基因大鼠中分离出脂肪间充质干细胞(AD-MSC)和骨髓间充质干细胞(BM-MSC),并使用温度响应培养皿将细胞制成片状。将 MSC 片用内镜移植到电凝和 DNBS 结肠炎模型的炎症区域。通过内镜评分和组织学分析验证了移植的效果。在电凝模型中,AD-MSC 组显示移植区域的溃疡面积明显减小。在 DNBS 结肠炎模型中,AD-MSC 组显示移植区域的炎症和结肠炎减轻。组织学分析显示,MSC 片在电凝和 DNBS 结肠炎模型中均成功附着于炎症黏膜。我们的结果表明,MSC 片的内镜移植可能是治疗 IBD 的一种新的有效的干细胞治疗模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e858/6063883/6b1de76ad20d/41598_2018_29617_Fig1_HTML.jpg

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