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鼠皮肤来源前体细胞向间充质和神经谱系分化的潜力及其在体内成骨诱导中的应用。

The potential of mouse skin-derived precursors to differentiate into mesenchymal and neural lineages and their application to osteogenic induction in vivo.

机构信息

Department of Oral Biochemistry and Program in Cancer and Developmental Biology, Seoul National University School of Dentistry, Seoul 110-749, Republic of Korea.

出版信息

Int J Mol Med. 2011 Dec;28(6):1001-11. doi: 10.3892/ijmm.2011.785. Epub 2011 Aug 29.

Abstract

Although previous studies indicate that skin-derived precursors (SKPs) are multipotent dermal precursors that share similarities with neural crest stem cells (NCSCs), a shared ability for multilineage differentiation toward neural crest lineages between SKPs and NCSCs has not been fully demonstrated. Here, we report the derivation of SKPs from adult mouse skin and their directed multilineage differentiation toward neural crest lineages. Under controlled in vitro conditions, mouse SKPs were propagated and directed toward peripheral nervous system lineages such as peripheral neurons and Schwann cells, and mesenchymal lineages, such as osteogenic, chondrogenic, adipogenic, and smooth muscle cells. To ask if SKPs could generate these same lineages in vivo, a mixture of SKP-derived mesenchymal stem cells and hydroxyapatite/tricalcium phosphate was transplanted into the rat calvarial defects. Over the ensuing 4 weeks, we observed formation of osteogenic structure in the calvarial defect without any evidence of teratomas. These findings demonstrate the multipotency of adult mouse SKPs to differentiate into neural crest lineages. In addition, SKP-derived mesenchymal stem cells represent an accessible, potentially autologous source of precursor cells for tissue-engineered bone repair.

摘要

虽然先前的研究表明皮肤源性前体细胞(SKPs)是具有与神经嵴干细胞(NCSCs)相似特性的多能真皮前体细胞,但 SKPs 和 NCSCs 之间是否具有向神经嵴谱系的多能性分化能力尚未得到充分证明。在这里,我们报告了从成年小鼠皮肤中分离出 SKPs,并将其定向分化为神经嵴谱系。在受控的体外条件下,小鼠 SKPs 被增殖并定向分化为外周神经系统谱系,如周围神经元和许旺细胞,以及间充质谱系,如成骨细胞、软骨细胞、脂肪细胞和平滑肌细胞。为了研究 SKPs 是否能在体内产生这些相同的谱系,将 SKP 衍生的间充质干细胞和羟基磷灰石/磷酸三钙混合物移植到大鼠颅骨缺损处。在接下来的 4 周内,我们观察到颅骨缺损处形成了成骨结构,没有任何畸胎瘤的证据。这些发现表明成年小鼠 SKPs 的多能性可以分化为神经嵴谱系。此外,SKP 衍生的间充质干细胞代表了一种可获得的、潜在的自体前体细胞来源,可用于组织工程骨修复。

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