Brief Report: Human Perivascular Stem Cells and Nel-Like Protein-1 Synergistically Enhance Spinal Fusion in Osteoporotic Rats.
Brief Report: Human Perivascular Stem Cells and Nel-Like Protein-1 Synergistically Enhance Spinal Fusion in Osteoporotic Rats.
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DOI：
10.1002/stem.2103
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Soo C
中科院分区：
文献类型：
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作者：
Lee S;Zhang X;Shen J;James AW;Chung CG;Hardy R;Li C;Girgius C;Zhang Y;Stoker D;Wang H;Wu BM;Peault B;Ting K;Soo C
自体骨移植被认为是脊柱融合的黄金标准。然而，由于成骨干细胞数量和骨微环境的功能有限，骨质疏松症患者不适合进行ABG。无论是在骨质疏松还是非骨质疏松的情况下，都需要基于干细胞的脊柱融合术。本研究的目的是确定人血管周围干细胞(HPSCs)在Nell-1成骨蛋白存在和不存在的情况下对骨质疏松患者脊柱融合的疗效。体外实验检测Nell-1对hPSCs成骨分化的影响。结果表明，Nell-1显著增加了骨质疏松和非骨质疏松供者hPSCs的成骨能力。接下来，在去卵巢的大鼠(n= 41)中，植入常规或高剂量的hPSCs支架，并加入或不加入NELL-1，进行脊柱融合。常规剂量的hPSCs或Nell-1人工触诊融合率仅为20%~37.5%。这些常规剂量此前已被证明在非骨质疏松大鼠脊柱融合中有效。值得注意的是，高剂量的hPSCs+Nell-1显著提高了骨质疏松大鼠的融合率，达到约83.3%。微计算机断层成像和量化进一步证实了高剂量hPSCs+Nell-1的固体骨融合。最后，组织学上，使用不脱钙的样本显示hPSCs直接参与了骨化。综上所述，hPSCs联合Nell-1可协同促进骨质疏松大鼠的脊柱融合，并具有作为治疗骨质疏松患者的新策略的巨大潜力。StemCells2015；33：3158-3163
Autologous bone grafts (ABGs) are considered as the gold standard for spinal fusion. However, osteoporotic patients are poor candidates for ABGs due to limited osteogenic stem cell numbers and function of the bone microenvironment. There is a need for stem cell-based spinal fusion of proven efficacy under either osteoporotic or nonosteoporotic conditions. The purpose of this study is to determine the efficacy of human perivascular stem cells (hPSCs), a population of mesenchymal stem cells isolated from adipose tissue, in the presence and absence of NELL-1, an osteogenic protein, for spinal fusion in the osteoporosis. Osteogenic differentiation of hPSCs with and without NELL-1 was tested in vitro. The results indicated that NELL-1 significantly increased the osteogenic potential of hPSCs in both osteoporotic and nonosteoporotic donors. Next, spinal fusion was performed by implanting scaffolds with regular or high doses of hPSCs, with or without NELL-1 in ovariectomized rats (n= 41). Regular doses of hPSCs or NELL-1 achieved the fusion rates of only 20%–37.5% by manual palpation. These regular doses had previously been shown to be effective in nonosteoporotic rat spinal fusion. Remarkably, the high dose of hPSCs+NELL-1 significantly improved the fusion rates among osteoporotic rats up to approximately 83.3%. Microcomputed tomography imaging and quantification further confirmed solid bony fusion with high dose hPSCs+NELL-1. Finally, histologically, direct in situ involvement of hPSCs in ossification was shown using undecalcified samples. To conclude, hPSCs combined with NELL-1 synergistically enhances spinal fusion in osteoporotic rats and has great potential as a novel therapeutic strategy for osteoporotic patients. StemCells2015;33:3158–3163