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首页> 外文期刊>Biomaterials >Neo-vascularization and bone formation mediated by fetal mesenchymal stem cell tissue-engineered bone grafts in critical-size femoral defects.
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Neo-vascularization and bone formation mediated by fetal mesenchymal stem cell tissue-engineered bone grafts in critical-size femoral defects.

机译：胎儿间充质干细胞组织工程化骨移植物介导的临界股骨缺损介导的新血管形成和骨形成。

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摘要

Tissue-engineered bone grafts (TEBG) require highly osteogenic cell sources for use in fracture repair applications. Compared to other sources of mesenchymal stem cells (MSC), human fetal MSC (hfMSC) have recently been shown to be more proliferative and osteogenic. We studied the functional performance of hfMSC-mediated TEBG in 7 mm rat femoral critical-sized bone defects (CSD). Dynamically-cultured and osteogenically-primed hfMSC seeded onto macroporous poly-epsilon-caprolactone tri-calcium phosphate scaffolds were transplanted into CSDs. After 12 weeks, hfMSC-mediated TEBG induced 2.1x more new bone formation (43.3+/-10.5 vs. 21.0+/-7.4 mm(3), p<0.05), with greater compact and woven bone, and a 9.8x increase in stiffness (3.9+/-1.7 vs. 0.4+/-0.3 mNm/degree, p<0.05) compared to acellular scaffolds, such that only animals transplanted with TEBG underwent full fracture repair of the CSD. Although hfMSC survived for <4 weeks, by 4 weeks they were associated with a 3.9x larger vasculature network in the defect area (35.2+/-11.1 vs. 6.5+/-3.6 mm(3)p<0.05), suggesting an important role for hfMSC in the promotion of neo-vasculogenesis. We speculate that hfMSC-mediated healing of the CSD by stimulating neo-vascularization through as yet undetermined mechanisms. This proof-of-principle study demonstrates the utility of primitive MSC for bone regeneration, and may be of relevance to vascularization in other areas of regenerative medicine.
机译：组织工程化的骨移植物（TEBG）需要高度成骨细胞来源才能用于骨折修复应用。与其他来源的间充质干细胞（MSC）相比，人类胎儿MSC（hfMSC）最近被证明具有更强的增殖性和成骨性。我们研究了hfMSC介导的TEBG在7 mm大鼠股骨临界大小骨缺损（CSD）中的功能性能。将动态培养并经成骨诱导的hfMSC接种到大孔聚ε-己内酯三磷酸钙支架上，然后移植到CSD中。 12周后，hfMSC介导的TEBG诱导了2.1倍的新骨形成（43.3 +/- 10.5对21.0 +/- 7.4 mm（3），p <0.05），具有更大的致密和编织骨，并增加了9.8倍与无细胞支架相比，其刚度（3.9 +/- 1.7对0.4 +/- 0.3 mNm /度，p <0.05）更高，因此只有移植了TEBG的动物才接受了CSD的完全骨折修复。尽管hfMSC存活时间小于4周，但到4周时，它们与缺陷区域的3.9倍大脉管系统网络相关联（35.2 +/- 11.1与6.5 +/- 3.6 mm（3）p <0.05），表明这一点很重要hfMSC在促进新血管生成中的作用。我们推测hfMSC介导的CSD愈合通过尚未确定的机制刺激新血管形成。这项原理验证研究证明了原始MSC在骨骼再生中的作用，并且可能与再生医学其他领域的血管形成有关。

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