HipOP mesenchymal population has high potential for repairing injured peripheral nerves

HipOP mesenchymal population has high potential for repairing injured peripheral nerves
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DOI:
10.1002/jcb.26684
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发表时间:
2018-06-01
影响因子:
4
通讯作者:
Hayashi,Mikako
Hayashi,Mikako
中科院分区:
生物学2区
文献类型:
--
作者:
Yamauchi,Yukako;Itoh,Shousaku;Hayashi,Mikako

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骨髓基质细胞(BMSCs)是一种异质性的间充质干细胞(MSCs)。最近,我们开发了一种简单的策略,用于富集具有分化成骨细胞、软骨细胞和脂肪细胞能力的MSC。在移植时,富含祖细胞的部分可以再生具有多个供体来源谱系的骨,因此被称为“高度纯化的骨祖细胞”(HipOP)。虽然我们以前的研究表明,HipOP富含MSC,并表现出比BMSC更高的分化成骨细胞,脂肪细胞和软骨细胞的潜力,但其分化为神经细胞的潜力尚未阐明。在这项研究中,我们评估了HipOPs作为神经干细胞来源的功效。神经球测定显示,由HipOPs形成的神经球具有自我更新能力,并且它们的尺寸通常大于由BMSCs形成的神经球。有限稀释法用于评估BMSC和HipOP中神经祖细胞的频率。结果表明,HipOPs中神经祖细胞的频率比BMSCs高120倍。此外,为了研究周围神经的体内再生潜力,我们修改了小鼠周围神经损伤实验模型,并证明了HipOPs在修复损伤的周围神经方面表现出更高的功效。这些发现表明,HipOP是再生疗法的有用细胞资源,例如在周围神经损伤的情况下。
Bone marrow stromal cells (BMSCs) are reportedly a heterogeneous population of mesenchymal stem cells (MSCs). Recently, we developed a simple strategy for the enrichment of MSCs with the capacity to differentiate into osteoblasts, chondrocytes, and adipocytes. On transplantation, the progenitor‐enriched fractions can regenerate the bone with multiple lineages of donor origin and are thus called “highly purified osteoprogenitors” (HipOPs). Although our previous studies have demonstrated that HipOPs are enriched with MSCs and exhibit a higher potential to differentiate into osteoblasts, adipocytes, and chondrocytes than BMSCs, their potential to differentiate into neural cells has not been clarified. In this study, we evaluated the efficacy of HipOPs as a resource of neural stem cells. The neurosphere assay showed that neurospheres formed by HipOPs exhibited self‐renewal ability and their size was generally larger than that of neurospheres formed by BMSCs. A limiting dilution assay was used to evaluate the frequency of neural progenitors in BMSCs and HipOPs. The results demonstrated that the frequency of neural progenitors in HipOPs was 120‐fold higher than that in BMSCs. Furthermore, to investigate the in vivo regenerative potential of the peripheral nerve, we modified a murine peripheral nerve injury experimental model and demonstrated that HipOPs exhibit a higher efficacy in repairing injured peripheral nerves. These findings suggest that HipOPs are a useful cell resource for regenerative therapies such as that in case of peripheral nerve injury.