Faculty of Medical Sciences, Department of Microbiology and Immunology, Center for Molecular Medicine and Stem Cell Research, University of Kragujevac, Kragujevac, Serbia.
Regenerative Processing Plant, LLC, Palm Harbor, FL, USA.
Anal Cell Pathol (Amst). 2017;2017:7492836. doi: 10.1155/2017/7492836. Epub 2017 Dec 19.
Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by the progressive destruction of small- and medium-sized intrahepatic bile ducts with resultant cholestasis and progressive fibrosis. Ursodeoxycholic acid and obethicholic acid are the only agents approved by the US Food and Drug Administration (FDA) for the treatment of PBC. However, for patients with advanced, end-stage PBC, liver transplantation is still the most effective treatment. Accordingly, the alternative approaches, such as mesenchymal stem cell (MSC) transplantation, have been suggested as an effective alternative therapy for these patients. Due to their immunomodulatory characteristics, MSCs are considered as promising therapeutic agents for the therapy of autoimmune liver diseases, including PBC. In this review, we have summarized the therapeutic potential of MSCs for the treatment of these diseases, emphasizing molecular and cellular mechanisms responsible for MSC-based effects in an animal model of PBC and therapeutic potential observed in recently conducted clinical trials. We have also presented several outstanding problems including safety issues regarding unwanted differentiation of transplanted MSCs which limit their therapeutic use. Efficient and safe MSC-based therapy for PBC remains a challenging issue that requires continuous cooperation between clinicians, researchers, and patients.
原发性胆汁性胆管炎（PBC）是一种慢性自身免疫性胆汁淤积性肝病，其特征为进行性破坏中小肝内胆管，导致胆汁淤积和进行性纤维化。熊去氧胆酸和奥贝胆酸是唯一经美国食品和药物管理局（FDA）批准用于治疗 PBC 的药物。然而，对于晚期终末期 PBC 患者，肝移植仍然是最有效的治疗方法。因此，已经提出了间充质干细胞（MSC）移植等替代方法作为这些患者的有效替代治疗方法。由于其免疫调节特性，MSC 被认为是治疗自身免疫性肝病（包括 PBC）的有前途的治疗剂。在这篇综述中，我们总结了 MSC 治疗这些疾病的治疗潜力，强调了 PBC 动物模型中负责 MSC 作用的分子和细胞机制以及最近进行的临床试验中观察到的治疗潜力。我们还提出了几个突出的问题，包括移植 MSC 发生意外分化的安全性问题，这限制了其治疗用途。用于 PBC 的高效和安全的 MSC 治疗仍然是一个具有挑战性的问题，需要临床医生、研究人员和患者之间的持续合作。
