Extracellular matrix derived from allogenic decellularized bone marrow mesenchymal stem cell sheets for the reconstruction of osteochondral defects in rabbits
Extracellular matrix derived from allogenic decellularized bone marrow mesenchymal stem cell sheets for the reconstruction of osteochondral defects in rabbits
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同种异体脱细胞骨髓间充质干细胞片细胞外基质用于兔骨软骨缺损的重建
DOI：
10.1016/j.actbio.2020.10.022
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发表时间：
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通讯作者：
Wu Buling
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作者：
Wang Zhifa;Han Leng;Sun Tianyu;Ma Junli;Sun Shuohui;Ma Limin;Wu Buling
合成高分子材料或脱细胞软骨基质制成的生物活性支架已被广泛应用于骨软骨再生。然而，潜在的免疫反应的风险和不可避免的供体发病率，这些支架限制了它们的实际应用。为了解决这些问题，从同种异体脱细胞骨髓间充质干细胞（BMSC）片衍生的生物细胞外基质（ECM）支架被建立用于骨软骨重建。诱导骨髓间充质干细胞形成细胞片。三种不同浓度的十二烷基硫酸钠（SDS），即0.5%，1%和3%，用于脱细胞这些BMSC片制备ECM。体外组织学和显微结构观察，然后将ECM支架植入兔骨软骨缺损中，评价其体内修复效果。用0.5%SDS处理不仅有效地去除了BMSCs，而且成功地保留了ECM的原始结构和生物活性成分。与1%和3%SDS组相比，组织学观察证实了骨软骨缺损的上级修复效果，包括同时再生的良好血管化的软骨下骨和无血管的关节软骨与天然组织整合在0.5% SDS组。RT-PCR结果显示，ECM支架在成骨条件下可促进BMSCs的成骨分化，在成软骨条件下可提高BMSCs的成软骨分化。0.5%SDS处理脱细胞的同种异体BMSC片增加了BMSC的募集，并显著改善了兔骨软骨缺损的再生，从而为关节软骨和软骨下骨的无细胞移植重建提供了一种有前景的方法。
Bioactive scaffolds from synthetical polymers or decellularized cartilage matrices have been widely used in osteochondral regeneration. However, the risks of potential immunological reactions and the inevitable donor morbidity of these scaffolds have limited their practical applications. To address these issues, a biological extracellular matrix (ECM) scaffold derived from allogenic decellularized bone marrow mesenchymal stem cell (BMSC) sheets was established for osteochondral reconstruction. BMSCs were induced to form cell sheets. Three different concentrations of sodium dodecyl sulfate (SDS), namely, 0.5%, 1%, and 3%, were used to decellularize these BMSC sheets to prepare the ECM. Histological and microstructural observations were performed in vitro and then the ECM scaffolds were implanted into osteochondral defects in rabbits to evaluate the repair effect in vivo. Treatment with 0.5% SDS not only efficiently removed BMSCs but also successfully preserved the original structure and bioactive components of the ECM When compared with the 1% and 3% SDS groups, histological observations substantiated the superior repair effect of osteochondral defects, including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular cartilage integrated with native tissues in the 0.5% SDS group. Moreover, RT-PCR indicated that ECM scaffolds could promote the osteogenic differentiation potential of BMSCs under osteogenic conditions while increasing the chondrogenic differentiation potential of BMSCs under chondrogenic conditions. Allogenic BMSC sheets decellularized with 0.5% SDS treatment increased the recruitment of BMSCs and significantly improved the regeneration of osteochondral defects in rabbits, thus providing a prospective approach for both articular cartilage and subchondral bone reconstruction with cell-free transplantation.