Stable subcutaneous cartilage regeneration of bone marrow stromal cells directed by chondrocyte sheet
Stable subcutaneous cartilage regeneration of bone marrow stromal cells directed by chondrocyte sheet
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软骨细胞片引导骨髓基质细胞稳定皮下软骨再生
DOI：
10.1016/j.actbio.2017.03.031
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发表时间：
2017-04-24
影响因子：
9.7
通讯作者：
Zhou, Guangdong
中科院分区：
文献类型：
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作者：
Li, Dan;Zhu, Lian;Zhou, Guangdong
体内生态位对干细胞的分化命运起着重要的调节作用。由于缺乏合适的软骨形成生态位，骨髓基质细胞（BMSCs）在皮下环境下稳定的软骨再生一直是一个巨大的挑战。本研究探讨了软骨细胞片在皮下环境下形成软骨生态位并保留BMSC工程软骨（BEC）软骨表型的可行性。将猪骨髓间充质干细胞植入生物可降解支架中，体外进行4周的成软骨诱导，形成BEC，分别包裹软骨细胞片（Sheet组）、脱细胞小肠粘膜下层（SIS组、SIS组）和不包裹BEC （Blank组），然后皮下植入裸鼠体内，追踪成软骨表型的维持情况。结果显示，薄片组所有构建物均表现出典型的软骨特征，有丰富的腔隙和软骨特异性基质沉积。随着体内植入时间的延长，这些样品变得更加成熟，除了一个没有完全包裹的样品外，在所有时间点几乎没有观察到骨化的迹象。Sheet组细胞标记结果进一步揭示了植入BEC直接参与软骨形成。SIS组和空白组各时间点标本均以骨化组织为主，少数标本有部分纤维形成。这些结果表明，软骨细胞片可以在皮下环境中形成软骨生态位，保持BEC的软骨表型，从而为基于干细胞的稳定异位软骨再生提供了新的研究模型。体内生态位对干细胞的分化命运起着重要的指导作用。由于缺乏合适的软骨形成生态位，骨髓基质细胞（BMSCs）在皮下环境下稳定的软骨再生一直是一个巨大的挑战。目前的研究表明，体外高密度培养软骨细胞生成的软骨细胞片可以在皮下环境中形成软骨生态位，并有效地保留体外BMSC工程软骨（vito - bec）的软骨表型。细胞示踪结果显示再生软骨主要来源于植入的体外bec。本研究不仅为微环境模拟提供了一种新的研究模型，而且为干细胞异位软骨稳定再生提供了一种有用的策略。(C) 2017材料学报Elsevier Ltd.出版。版权所有。
In vivo niche plays an important role in regulating differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. This study explored the feasibility that chondrocyte sheet created chondrogenic niche retained chondrogenic phenotype of BMSC engineered cartilage (BEC) in subcutaneous environments. Porcine BMSCs were seeded into biodegradable scaffolds followed by 4 weeks of chondrogenic induction in vitro to form BEC, which were wrapped with chondrocyte sheets (Sheet group), acellular small intestinal submucosa (SIS, SIS group), or nothing (Blank group) respectively and then implanted subcutaneously into nude mice to trace the maintenance of chondrogenic phenotype. The results showed that all the constructs in Sheet group displayed typical cartilaginous features with abundant lacunae and cartilage specific matrices deposition. These samples became more mature with prolonged in vivo implantation, and few signs of ossification were observed at all time points except for one sample that had not been wrapped completely. Cell labeling results in Sheet group further revealed that the implanted BEC directly participated in cartilage formation. Samples in both SIS and Blank groups mainly showed ossified tissue at all time points with partial fibrogenesis in a few samples. These results suggested that chondrocyte sheet could create a chondrogenic niche for retaining chondrogenic phenotype of BEC in subcutaneous environment and thus provide a novel research model for stable ectopic cartilage regeneration based on stem cells.Statement of significanceIn vivo niche plays an important role in directing differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. The current study demonstrated that chondrocyte sheet generated by high-density culture of chondrocytes in vitro could cearte a chondrogenic niche in subcutaneous environment and efficiently retain the chondrogenic phenotype of in vitro BMSC engineered cartilage (vitro-BEC). Furthermore, cell tracing results revealed that the regenerated cartilage mainly derived from the implanted vitro-BEC. The current study not only proposes a novel research model for microenvironment simulation but also provides a useful strategy for stable ectopic cartilage regeneration of stem cells. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.