Department of Research and Academic Affairs, Larkin Community Hospital, Miami, FL, USA.
I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation.
Stem Cell Res Ther. 2022 May 8;13(1):192. doi: 10.1186/s13287-022-02825-z.
Recently, mesenchymal stromal cells (MSCs) and their derivative exosome have become a promising approach in the context of liver diseases therapy, in particular, acute liver failure (ALF). In addition to their differentiation into hepatocytes in vivo, which is partially involved in liver regeneration, MSCs support liver regeneration as a result of their appreciated competencies, such as antiapoptotic, immunomodulatory, antifibrotic, and also antioxidant attributes. Further, MSCs-secreted molecules inspire hepatocyte proliferation in vivo, facilitating damaged tissue recovery in ALF. Given these properties, various MSCs-based approaches have evolved and resulted in encouraging outcomes in ALF animal models and also displayed safety and also modest efficacy in human studies, providing a new avenue for ALF therapy. Irrespective of MSCs-derived exosome, MSCs-based strategies in ALF include administration of native MSCs, genetically modified MSCs, pretreated MSCs, MSCs delivery using biomaterials, and also MSCs in combination with and other therapeutic molecules or modalities. Herein, we will deliver an overview regarding the therapeutic effects of the MSCs and their exosomes in ALF. As well, we will discuss recent progress in preclinical and clinical studies and current challenges in MSCs-based therapies in ALF, with a special focus on in vivo reports.
最近，间充质基质细胞（MSCs）及其衍生的外泌体在肝脏疾病治疗方面，尤其是急性肝衰竭（ALF）方面，成为一种很有前途的方法。除了在体内部分参与肝再生的向肝细胞分化之外，MSCs 还具有抗细胞凋亡、免疫调节、抗纤维化和抗氧化等特性，从而支持肝再生。此外，MSCs 分泌的分子在体内激发肝细胞增殖，促进 ALF 中受损组织的恢复。鉴于这些特性，各种基于 MSCs 的方法已经发展起来，并在 ALF 动物模型中取得了令人鼓舞的结果，在人体研究中也显示出安全性和适度的疗效，为 ALF 治疗提供了新途径。无论是否来源于 MSCs 的外泌体，MSCs 在 ALF 中的应用策略包括给予原代 MSCs、基因修饰的 MSCs、预处理的 MSCs、使用生物材料输送 MSCs，以及 MSCs 与其他治疗分子或方式的联合应用。本文将概述 MSCs 及其外泌体在 ALF 中的治疗作用。同时，我们将讨论 ALF 中基于 MSCs 的治疗的临床前和临床研究的最新进展以及当前面临的挑战，特别关注体内研究报告。
