Division of Biomedical Research and Development, Institute of Biomedical Sciences, Iwate Medical University, Morioka, Japan.
Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
Adv Exp Med Biol. 2018;1103:219-241. doi: 10.1007/978-4-431-56847-6_12.
Cellular compensation from extrahepatic resources is expected to improve the prognosis of liver diseases. Currently, liver dysfunction is treated by a variety of modalities including drugs, cytokines, vascular interventions, energy devices, surgery, and liver transplantation; however, in recent years there have been few significant advancements in treatment efficacy. A next-generation therapeutic strategy for liver disease, cellular compensatory therapy (i.e., cell therapy), is now being considered for clinical practice. Liver dysfunction is attributed to a lack of sufficient functional cells. However, processes involved in recovery of liver function are not fully elucidated, which has complicated the interpretation of treatment effects at the cellular level. Our genotyping study of living donor liver transplantation revealed that a variety of graft liver tissues contained the donor genotype, indicating that extrahepatic cells had differentiated into liver component cells during liver regeneration. Multilineage-differentiating stress-enduring (Muse) cells appear to be a strong candidate for extrahepatic resources that can contribute to liver regeneration. Muse cells are defined as stage-specific embryonic antigen 3-expressing cells that contribute to tissue regeneration and have the potential to differentiate into three germ layers. The significant advantage of Muse cells over other "pluripotent cells" is that Muse cells are present in bone marrow/blood as well as a variety of connective tissues, which provides safety and ethical advantages for clinical applications. Here, we review current therapeutic topics in liver diseases and discuss the potential for cell therapy using Muse cells based on our recent studies of Muse cell administration in a mouse model of physical partial hepatectomy.
从肝外资源进行细胞补偿有望改善肝脏疾病的预后。目前，肝功能障碍的治疗方法有多种，包括药物、细胞因子、血管介入、能量装置、手术和肝移植；然而，近年来治疗效果鲜有显著进展。细胞补偿治疗（即细胞疗法）作为肝脏疾病的下一代治疗策略，目前正在考虑用于临床实践。肝功能障碍归因于缺乏足够的功能细胞。然而，肝功能恢复的过程尚未完全阐明，这使得在细胞水平上解释治疗效果变得复杂。我们对活体供肝移植的基因分型研究表明，各种供体肝组织都含有供体基因型，这表明在肝再生过程中，肝外细胞已分化为肝成分细胞。多谱系分化应激耐受（Muse）细胞似乎是一种强大的肝外资源候选物，可促进肝再生。Muse 细胞被定义为表达阶段特异性胚胎抗原 3 的细胞，有助于组织再生，并具有分化为三个胚层的潜力。Muse 细胞相对于其他“多能细胞”的显著优势在于，Muse 细胞存在于骨髓/血液以及各种结缔组织中，这为临床应用提供了安全性和伦理学优势。在这里，我们回顾了肝脏疾病的当前治疗主题，并根据我们最近在物理部分肝切除术小鼠模型中施用 Muse 细胞的研究，讨论了使用 Muse 细胞进行细胞治疗的潜力。
