Liver Regeneration Supported by Muse Cells.

Liver Regeneration Supported by Muse Cells.
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DOI:
10.1007/978-4-431-56847-6_12
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发表时间:
2018
影响因子:
--
通讯作者:
S. Nishizuka;Yuji Suzuki;Hirokatsu Katagiri;Y. Takikawa
S. Nishizuka;Yuji Suzuki;Hirokatsu Katagiri;Y. Takikawa
中科院分区:
医学4区
文献类型:
--
作者:
S. Nishizuka;Yuji Suzuki;Hirokatsu Katagiri;Y. Takikawa

文献摘要

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肝外资源的细胞补偿有望改善肝病的预后。目前,肝功能障碍的治疗方法有多种,包括药物、细胞因子、血管干预、能量装置、手术和肝移植等。然而,近年来治疗效果几乎没有取得重大进展。下一代肝病治疗策略——细胞补偿疗法(即细胞疗法)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,肝功能恢复过程尚未完全阐明,这使得细胞水平上治疗效果的解释变得复杂。我们对活体肝移植的基因分型研究表明,多种移植肝组织均含有供体基因型,表明肝再生过程中肝外细胞已分化为肝成分细胞。多谱系分化的耐应激(Muse)细胞似乎是有助于肝脏再生的肝外资源的有力候选者。 Muse 细胞被定义为阶段特异性胚胎抗原 3 表达细胞,有助于组织再生并具有分化成三个胚层的潜力。 Muse细胞相对于其他“多能细胞”的显着优势在于Muse细胞存在于骨髓/血液以及多种结缔组织中,这为临床应用提供了安全性和伦理优势。在这里,我们回顾了当前肝脏疾病的治疗主题,并根据我们最近在物理部分肝切除小鼠模型中施用 Muse 细胞的研究,讨论了使用 Muse 细胞进行细胞治疗的潜力。
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.