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Generation of Multipotent Stem Cells from Adult Human Peripheral Blood Following the Treatment with Platelet-Derived Mitochondria.
Cells ( IF 6 ) Pub Date : 2020-05-29 , DOI: 10.3390/cells9061350
Haibo Yu 1 , Wei Hu 1 , Xiang Song 1 , Yong Zhao 1
Affiliation  

Autologous stem cells are highly preferred for cellular therapy to treat human diseases. Mitochondria are organelles normally located in cytoplasm. Our recent studies demonstrated the differentiation of adult peripheral blood-derived insulin-producing cells (designated PB-IPC) into hematopoietic-like cells after the treatment with platelet-derived mitochondria. To further explore the molecular mechanism and their therapeutic potentials, through confocal and electron microscopy, we found that mitochondria enter cells and directly penetrate the nucleus of PB-IPC after the treatment with platelet-derived mitochondria, where they can produce profound epigenetic changes as demonstrated by RNA-seq and PCR array. Ex vivo functional studies established that mitochondrion-induced PB-IPC (miPB-IPC) can give rise to retinal pigment epithelium (RPE) cells and neuronal cells in the presence of different inducers. Further colony analysis highlighted the multipotent capability of the differentiation of PB-IPC into three-germ layer-derived cells. Therefore, these data indicate a novel function of mitochondria in cellular reprogramming, leading to the generation of autologous multipotent stem cells for clinical applications.

中文翻译:

用血小板衍生的线粒体治疗后,从成年人类外周血中生成多能干细胞。

自体干细胞非常适合用于治疗人类疾病的细胞疗法。线粒体是通常位于细胞质中的细胞器。我们最近的研究表明,用血小板衍生的线粒体治疗后,成人外周血来源的胰岛素生成细胞(称为PB-IPC)分化为造血样细胞。为了进一步探讨分子机制及其治疗潜力,通过共聚焦和电子显微镜观察,我们发现线粒体经过血小板衍生的线粒体处理后进入细胞并直接穿透PB-IPC的核,从而可以产生深刻的表观遗传变化。通过RNA-seq和PCR阵列。体外功能研究确定,线粒体诱导的PB-IPC(miPB-IPC)可以在存在不同诱导剂的情况下产生视网膜色素上皮(RPE)细胞和神经元细胞。进一步的菌落分析强调了PB-IPC分化为三胚层来源的细胞的多能能力。因此,这些数据表明线粒体在细胞重编程中具有新功能,从而导致了用于临床应用的自体多能干细胞的产生。
更新日期:2020-05-29
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