Human Perivascular Stem Cell-Based Bone Graft Substitute Induces Rat Spinal Fusion
Human Perivascular Stem Cell-Based Bone Graft Substitute Induces Rat Spinal Fusion
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DOI：
10.5966/sctm.2014-0027
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发表时间：
2014-10-01
影响因子：
6
通讯作者：
Soo, Chia
中科院分区：
文献类型：
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作者：
Chung, Choon G.;James, Aaron W.;Soo, Chia
脂肪组织是间充质干细胞（MSC）的一个有吸引力的来源，因为它的丰富性和可及性。我们以前已经定义了一个称为血管周围干细胞（PSC）的天然MSC群体，从不同的人体组织，包括脂肪组织中纯化。人PSC（hPSC）是由周细胞（CD 146 + CD 34-CD 45-）和外膜细胞（CD 146-CD 34 + CD 45-）组成的二分细胞群，其通过荧光激活细胞分选分离并且具有与培养鉴定的MSC相同的性质。我们先前的研究表明，与样品匹配的未纯化群体（称为基质血管部分）相比，hPSC表现出改善的骨形成;然而，尚不清楚hPSC在脊柱融合模型中是否有效。为了研究，我们在大鼠后外侧腰椎融合模型中评估了新鲜分选的hPSC的成骨潜力，而没有培养扩增和分化。我们比较了植入的hPSC的增加剂量以评估剂量依赖性功效。通过手动触诊和显微计算机断层扫描评估，所有hPSC治疗组均诱导成功的脊柱融合。计算机生物力学模拟（有限元分析）进一步证实了hPSC治疗的骨融合。组织学分析显示hPSC处理的样品中有稳健的软骨内骨化。最后，我们证实植入的hPSC确实分化成成骨细胞和骨细胞;然而，大多数新骨形成是宿主来源的。这些结果表明，植入的hPSC通过直接和旁分泌机制正向调节骨形成。总之，hPSC是一种容易获得的MSC群体，其有效地形成骨而不需要培养或预分化。因此，基于hPSC的产品显示出在临床骨再生和修复方面的未来努力的前景。
Adipose tissue is an attractive source of mesenchymal stem cells (MSCs) because of its abundance and accessibility. We have previously defined a population of native MSCs termed perivascular stem cells (PSCs), purified from diverse human tissues, including adipose tissue. Human PSCs (hPSCs) are a bipartite cell population composed of pericytes (CD146+CD34-CD45-) and adventitial cells (CD146-CD34+CD45-), isolated by fluorescence-activated cell sorting and with properties identical to those of culture identified MSCs. Our previous studies showed that hPSCs exhibit improved bone formation compared with a sample-matched unpurified population (termed stromal vascular fraction); however, it is not known whether hPSCs would be efficacious in a spinal fusion model. To investigate, we evaluated the osteogenic potential of freshly sorted hPSCs without culture expansion and differentiation in a rat model of posterolateral lumbar spinal fusion. We compared increasing dosages of implanted hPSCs to assess for dose-dependent efficacy. All hPSC treatment groups induced successful spinal fusion, assessed by manual palpation and microcomputed tomography. Computerized biomechanical simulation (finite element analysis) further demonstrated bone fusion with hPSC treatment. Histological analyses showed robust endochondral ossification in hPSC-treated samples. Finally, we confirmed that implanted hPSCs indeed differentiated into osteoblasts and osteocytes; however, the majority of the new bone formation was of host origin. These results suggest that implanted hPSCs positively regulate bone formation via direct and paracrine mechanisms. In summary, hPSCs are a readily available MSC population that effectively forms bone without requirements for culture or predifferentiation. Thus, hPSC-based products show promise for future efforts in clinical bone regeneration and repair.