In vitro osteogenic induction of bone marrow mesenchymal stem cells with a decellularized matrix derived from human adipose stem cells and in vivo implantation for bone regeneration.
In vitro osteogenic induction of bone marrow mesenchymal stem cells with a decellularized matrix derived from human adipose stem cells and in vivo implantation for bone regeneration.
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DOI：
10.1039/c6tb03150a
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发表时间：
2017-03
期刊：
影响因子：
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通讯作者：
Wei Wei-Wei;Jipeng Li;Shuo Chen;Mingjiao Chen;Qing Xie;Hao Sun;Jing Ruan;Huifang Zhou;
中科院分区：
文献类型：
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作者：
Wei Wei-Wei;Jipeng Li;Shuo Chen;Mingjiao Chen;Qing Xie;Hao Sun;Jing Ruan;Huifang Zhou;
组织工程技术采用间充质干细胞与支架材料相结合的方法，为组织再生提供了一种很有前途的策略。人脂肪源性干细胞（hADSCs）因其良好的成骨潜能在骨工程领域受到广泛关注。细胞外基质（ECM）作为物理支持对于干细胞龛是至关重要的，并且已知能够维持干细胞特性。本研究从ADSCs中制备了细胞外基质（ECM），并将其命名为ADM。体外实验表明，ADM能显著促进骨髓源性干细胞（BMSCs）的增殖，并具有较强的成骨刺激作用。结果表明，成骨细胞碱性磷酸酶（ALP）活性、茜素红S（ARS）染色、成骨基因标志物和蛋白质表达均显著上调。接下来，我们开发了一种涂有ADM的聚（癸二酰甘油二酯）（PSeD）网状支架，并评估了其创造成骨微环境的能力。将骨髓基质细胞在复合支架上进行体外成骨分化。结果表明，复合支架比单纯的PSeD支架更有利于成骨。将骨髓间充质干细胞种植于PSeD/ADM支架上，修复大鼠颅骨临界缺损，显微CT、荧光标记和组织学观察证实，PSeD/ADM支架修复效果明显增强。综上所述，ADM可促进BMSCs的增殖和成骨，ADM和PSeD联合应用可协同促进骨形成，为骨再生提供了一种新的方案。
Tissue engineering technology that adopts mesenchymal stem cells combined with scaffolds presents a promising strategy for tissue regeneration. Human adipose-derived stem cells (hADSCs) have attracted considerable attention in bone engineering for their osteogenic potential. The extracellular matrix (ECM) is critical for the stem cell niche as a physical support and is known to be able to maintain stem cell properties. In this study, the ECM derived from ADSCs was produced and termed the ADM. The ADM was demonstrated to markedly promote proliferation of bone marrow derived stem cells (BMSCs) and exhibited strongly osteogenic simulative effects in vitro. The results showed that alkaline phosphatase (ALP) activity, Alizarin red S (ARS) staining, osteogenic gene markers and proteins were significantly up-regulated. Next, we developed a poly(sebacoyl diglyceride) (PSeD) mesh scaffold coated with the ADM and evaluated its capacity to create an osteogenic microenvironment. BMSCs were cultured on the composite scaffolds and subjected to osteogenic differentiation in vitro. The results showed that the composite scaffolds facilitated the osteogenesis more than a simple PSeD scaffold. Then the PSeD/ADM scaffold seeded with BMSCs was used to repair critical-sized calvarial defects in rats, which significantly enhanced the reparative effects as confirmed via micro-CT, sequential fluorescent labeling and histological observation. In conclusion, we demonstrated that the ADM could promote both proliferation and osteogenesis of BMSCs, and the combination of ADM and PSeD synergistically stimulated bone formation, which may provide a novel scheme for bone regeneration.