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Chondrogenic and BMP-4 primings confer osteogenesis potential to human cord blood mesenchymal stromal cells delivered with biphasic calcium phosphate ceramics

机译:软骨增生和BMP-4底漆赋予人脐带血间充质细胞的骨肉型潜力,其用双相磷酸钙陶瓷输送

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摘要

Abstract Bone marrow mesenchymal stem/stromal cells (BMSCs) show great promise for bone repair, however they are isolated by an invasive bone marrow harvest and their regenerative potential decreases with age. Conversely, cord blood can be collected non-invasively after birth and contains MSCs (CBMSCs) that can be stored for future use. However, whether CBMSCs can replace BMSCs targeting bone repair is unknown. This study evaluates the in vitro osteogenic potential of unprimed, osteogenically primed, or chondrogenically primed CBMSCs and BMSCs and their in vivo bone forming capacity following ectopic implantation on biphasic calcium phosphate ceramics in nude mice. In vitro, alkaline phosphatase (intracellular, extracellular, and gene expression), and secretion of osteogenic cytokines (osteoprotegerin and osteocalcin) was significantly higher in BMSCs compared with CBMSCs, while CBMSCs demonstrated superior chondrogenic differentiation and secretion of interleukins IL-6 and IL-8. BMSCs yielded significantly more cell engraftment and ectopic bone formation compared to CBMSCs. However, priming of CBMSCs with either chondrogenic or BMP-4 supplements led to bone formation by CBMSCs. This study is the first direct quantification of the bone forming abilities of BMSCs and CBMSCs in vivo and, while revealing the innate superiority of BMSCs for bone repair, it provides avenues to induce osteogenesis by CBMSCs.
机译:摘要骨髓间充质茎/基质细胞(BMSCs)表现出对骨骼修复的巨大希望,然而,它们被侵入性骨髓收获隔离,并且它们随着年龄的增长而降低它们的再生潜力。相反,出生后可以非侵入地收集脐带血,并包含可以存储以供将来使用的MSC(CBMSCS)。但是,CBMSCs是否可以取代靶向骨骼修复的BMSC。该研究评估未预期的,骨开采的CBMSCs和BMSCs的体外成骨潜力,以及在裸鼠双相磷酸钙陶瓷上的异位植入后的体内骨形成能力。在体外,碱性磷酸酶(细胞内,细胞外和基因表达)和BMSC的分泌物与CBMSCs相比,BMSCs显着高得多,而CBMSCs展示了过于亲属的软骨内分化和白细胞介素IL-6和IL的分泌8。与CBMSCs相比,BMSCs产生更多细胞植入和异位骨形成。然而,CBM​​SCS的灌注具有软骨原或BMP-4补充剂导致CBMSCs的骨形成。本研究是第一次直接定量BMSCs和CBMSCs在体内的骨形成能力,同时揭示了BMSCs用于骨骼修复的先天优越性,它为CBMSCs提供了诱导成骨的途径。

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