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间充质干细胞(MSCs)为基础的细胞疗法治疗炎症性肠病(IBD)的治疗潜力。

Therapeutic potential of mesenchymal stem/stromal cells (MSCs)-based cell therapy for inflammatory bowel diseases (IBD) therapy.

机构信息

Department of Basic Sciences, Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan.

I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.

出版信息

Eur J Med Res. 2023 Jan 27;28(1):47. doi: 10.1186/s40001-023-01008-7.

Abstract

Recently, mesenchymal stem/stromal cells (MSCs) therapy has become an emerging therapeutic modality for the treatment of inflammatory bowel disease (IBD), given their immunoregulatory and pro-survival attributes. MSCs alleviate dysregulated inflammatory responses through the secretion of a myriad of anti-inflammatory mediators, such as interleukin 10 (IL-10), transforming growth factor-β (TGFβ), prostaglandin E2 (PGE2), tumor necrosis factor-stimulated gene-6 (TSG-6), etc. Indeed, MSC treatment of IBD is largely carried out through local microcirculation construction, colonization and repair, and immunomodulation, thus alleviating diseases severity. The clinical therapeutic efficacy relies on to the marked secretion of various secretory molecules from viable MSCs via paracrine mechanisms that are required for gut immuno-microbiota regulation and the proliferation and differentiation of surrounding cells like intestinal epithelial cells (IECs) and intestinal stem cells (ISCs). For example, MSCs can induce IECs proliferation and upregulate the expression of tight junction (TJs)-associated protein, ensuring intestinal barrier integrity. Concerning the encouraging results derived from animal studies, various clinical trials are conducted or ongoing to address the safety and efficacy of MSCs administration in IBD patients. Although the safety and short-term efficacy of MSCs administration have been evinced, the long-term efficacy of MSCs transplantation has not yet been verified. Herein, we have emphasized the illumination of the therapeutic capacity of MSCs therapy, including naïve MSCs, preconditioned MSCs, and also MSCs-derived exosomes, to alleviate IBD severity in experimental models. Also, a brief overview of published clinical trials in IBD patients has been delivered.

摘要

最近,间充质干细胞(MSCs)疗法因其具有免疫调节和生存促进特性,已成为治疗炎症性肠病(IBD)的新兴治疗方法。MSCs 通过分泌大量抗炎介质,如白细胞介素 10(IL-10)、转化生长因子-β(TGFβ)、前列腺素 E2(PGE2)、肿瘤坏死因子刺激基因-6(TSG-6)等,缓解失调的炎症反应。事实上,MSC 治疗 IBD 主要通过局部微循环构建、定植和修复以及免疫调节来实现,从而缓解疾病严重程度。临床治疗效果依赖于活 MSC 通过旁分泌机制大量分泌各种分泌分子,这些分子对于肠道免疫微生物群的调节以及周围细胞(如肠上皮细胞(IECs)和肠干细胞(ISCs))的增殖和分化是必需的。例如,MSCs 可以诱导 IECs 增殖并上调紧密连接(TJs)相关蛋白的表达,从而确保肠道屏障的完整性。鉴于动物研究中得出的令人鼓舞的结果,目前正在进行或正在进行各种临床试验,以解决 MSCs 在 IBD 患者中的安全性和疗效问题。虽然已经证明了 MSCs 给药的安全性和短期疗效,但 MSCs 移植的长期疗效尚未得到验证。在这里,我们强调了 MSCs 治疗(包括未成熟 MSCs、预处理 MSCs 和 MSCs 衍生的外泌体)在减轻实验模型中 IBD 严重程度方面的治疗能力。此外,还简要介绍了发表的 IBD 患者临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9652/9881387/04ec3451e07b/40001_2023_1008_Fig1_HTML.jpg

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