Developmental-Like Bone Regeneration by Human Embryonic Stem Cell-Derived Mesenchymal Cells
Developmental-Like Bone Regeneration by Human Embryonic Stem Cell-Derived Mesenchymal Cells
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DOI：
10.1089/ten.tea.2013.0321
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发表时间：
2014-01-01
影响因子：
4.1
通讯作者：
Goldberg, A. Jon
中科院分区：
文献类型：
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作者：
Kuhn, Liisa T.;Liu, Yongxing;Goldberg, A. Jon
采用胶原/羟基磷灰石支架植入免疫缺陷小鼠颅骨缺损，评价了人胚胎干细胞来源的间充质样细胞（hESC-MCs）的体内成骨潜能。这项研究是新颖的，因为在植入前没有对细胞进行成骨或软骨分化。6周后，x射线、微ct和组织学分析显示，hESC-MCs持续形成高度血管化的新骨，桥接骨缺损并与宿主骨无缝结合。植入的hESC-MCs通过软骨内成骨途径原位分化为功能性肥大软骨细胞、成骨细胞和形成新骨组织的骨细胞。人类细胞直接参与骨形态发生的证据通过两个单独的试验得到证实：Alu和人类线粒体抗原阳性染色，结合组织学上证实的新骨区域中人类骨唾液蛋白的共定位表达。颅骨缺损中大量的新骨和hESC-MCs的直接参与远远超过了先前的研究和对照成人hMSCs。这项研究代表了骨组织工程的关键一步，因为新骨形成的体积大，血管丰富，可重复性好，并且发现在植入前不将这些祖细胞过度注入特定谱系是有利的。hesc - mc能够再现间充质发育途径，并且能够半自主地修复骨缺损，而无需植入前分化为骨祖细胞或软骨祖细胞。
The in vivo osteogenesis potential of mesenchymal-like cells derived from human embryonic stem cells (hESC-MCs) was evaluated in vivo by implantation on collagen/hydroxyapatite scaffolds into calvarial defects in immunodeficient mice. This study is novel because no osteogenic or chondrogenic differentiation protocols were applied to the cells prior to implantation. After 6 weeks, X-ray, microCT, and histological analysis showed that the hESC-MCs had consistently formed a highly vascularized new bone that bridged the bone defect and seamlessly integrated with host bone. The implanted hESC-MCs differentiated in situ to functional hypertrophic chondrocytes, osteoblasts, and osteocytes forming new bone tissue via an endochondral ossification pathway. Evidence for the direct participation of the human cells in bone morphogenesis was verified by two separate assays: with Alu and by human mitochondrial antigen positive staining in conjunction with co-localized expression of human bone sialoprotein in histologically verified regions of new bone. The large volume of new bone in a calvarial defect and the direct participation of the hESC-MCs far exceeds that of previous studies and that of the control adult hMSCs. This study represents a key step forward for bone tissue engineering because of the large volume, vascularity, and reproducibility of new bone formation and the discovery that it is advantageous to not over-commit these progenitor cells to a particular lineage prior to implantation. The hESC-MCs were able to recapitulate the mesenchymal developmental pathway and were able to repair the bone defect semi-autonomously without preimplantation differentiation to osteo-or chondroprogenitors.