Kidney regeneration using developing xenoembryo
Kidney regeneration using developing xenoembryo
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DOI：
10.1097/mot.0000000000000176
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发表时间：
2015-04
影响因子：
2.2
通讯作者：
Akira Fukui;T. Yokoo
中科院分区：
文献类型：
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作者：
Akira Fukui;T. Yokoo
本文综述了肾脏再生的最新进展，重点介绍了我们之前使用发育中的异种胚胎分化人间充质干细胞（hMSCs）的研究。本文概述了该方法的原理、最新进展以及与肾脏再生相关的局限性和挑战。我们的主要研究目标是从透析患者来源的hMSCs中生成新肾脏。我们之前的研究表明，表达神经胶质细胞源性神经营养因子的hMSCs可以在发育中的哺乳动物胚胎中分化为功能性嵌合肾细胞。最近，我们通过引入自杀基因成功地消除了转基因雌激素受体- e2f转录因子1 （ER-E2F1）小鼠的异种组织。我们还发现来自透析患者的间充质干细胞可以用于肾脏再生。利用囊胚互补策略，将小鼠多能干细胞注入敲除spalt-like transcription factor 1 （Sall1）的小鼠囊胚中，生成嵌合肾细胞。肾组织可由人小鼠多能干细胞或MSCs通过几种方法生成。再生肾组织的大小和功能不符合临床应用的移植要求。尽管肾脏再生仍存在许多突出的问题，包括伦理问题和嵌合结构的形成，但完全由透析患者来源的细胞生成新肾脏有望在未来成为现实。
Purpose of reviewWe provide an overview of the recent progress in kidney regeneration with a particular focus on our previous study, which used developing xenoembryos for differentiating human mesenchymal stem cells (hMSCs). The principle of the methodology, recent advances, and limitations and challenges associated with kidney regeneration are outlined. Recent findingsOur primary study objective is to generate neokidney from dialysis patient-derived hMSCs. We previously showed that glial cell-derived neurotrophic factor-expressing hMSCs can differentiate into functional chimeric nephrons in developing mammalian embryos. Recently, we succeeded in eliminating xenotissues in transgenic oestrogen receptor-E2F transcription factor 1 (ER-E2F1) mice by introducing a suicide gene. We also showed MSCs derived from dialysis patients can be used for kidney regeneration. Blastocyst complementation strategy was used to generate chimeric nephrons by injecting mouse pluripotent stem cells into spalt-like transcription factor 1 (Sall1) knockout mouse blastocysts. SummaryKidney tissue can be generated from human mouse pluripotent stem cells or MSCs by several methods. The size and function of regenerated kidney tissue do not meet the transplantation requirements for clinical applications. Although many outstanding problems remain for kidney regeneration, including ethical issues and the formation of chimeric structures, the neokidney generation exclusively from dialysis patient-derived cells is expected to be a reality in the future.