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Tissue Constructs with Human Adipose-Derived Mesenchymal Stem Cells to Treat Bone Defects in Rats

机译:人脂肪间充质干细胞的组织构建物治疗大鼠骨缺损

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摘要

The use of porous scaffolds created by additive manufacturing is considered a viable approach for the regeneration of critical-size bone defects. This paper investigates the xenotransplantation of polycaprolactone (PCL) tissue constructs seeded with differentiated and undifferentiated human adipose-derived mesenchymal stem cells (hADSCs) to treat calvarial critical-sized defect in Wistar rats. PCL scaffolds without cells were also considered. In vitro and in vivo biological evaluations were performed to assess the feasibility of these different approaches. In the case of cell seeded scaffolds, it was possible to observe the presence of hADSCs in the rat tissue contributing directly (osteoblasts) and indirectly (stimulation by paracrine factors) to tissue formation, organization and mineralization. The presence of bone morphogenetic protein-2 (BMP-2) in the rat tissue treated with cell-seeded PCL scaffolds suggests that the paracrine factors of undifferentiated hADSC cells could stimulate BMP-2 production by surrounding cells, leading to osteogenesis. Moreover, BMP-2 acts synergistically with growth factors to induce angiogenesis, leading to higher numbers of blood vessels in the groups containing undifferentiated and differentiated hADSCs.
机译:通过增材制造产生的多孔支架被认为是再生临界尺寸骨缺损的可行方法。本文研究了聚己内酯(PCL)组织构建体的异种移植,该组织构建体植入了分化的和未分化的人类脂肪间充质干细胞(hADSCs),以治疗Wistar大鼠的颅骨临界大小缺陷。还考虑了无细胞的PCL支架。进行了体外和体内生物学评估,以评估这些不同方法的可行性。对于细胞接种的支架,可以观察到大鼠组织中存在hADSCs,它们直接(成骨细胞)和间接(通过旁分泌因子刺激)促成组织形成,组织和矿化。用细胞接种的PCL支架处理的大鼠组织中骨形态发生蛋白2(BMP-2)的存在表明未分化的hADSC细胞的旁分泌因子可以刺激周围细胞产生BMP-2,导致成骨。此外,BMP-2与生长因子协同作用以诱导血管生成,从而导致包含未分化和分化的hADSCs的组中的血管数量增加。

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