Platelet-Derived Growth Factor BB Enhances Osteogenesis of Adipose-Derived But Not Bone Marrow-Derived Mesenchymal Stromal/Stem Cells.
Platelet-Derived Growth Factor BB Enhances Osteogenesis of Adipose-Derived But Not Bone Marrow-Derived Mesenchymal Stromal/Stem Cells.
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DOI：
10.1002/stem.2060
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Grayson WL
中科院分区：
文献类型：
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作者：
Hung BP;Hutton DL;Kozielski KL;Bishop CJ;Naved B;Green JJ;Caplan AI;Gimble JM;Dorafshar AH;Grayson WL
使用间充质干细胞的组织工程学在再生严重尺寸的骨缺损方面具有很大的前景。虽然骨髓来源的间充质干细胞（MSC）是用于该应用的最广泛研究的基质/干细胞类型，但其在骨髓中的稀有性和痛苦的分离程序促使人们研究替代细胞来源。脂肪来源的基质/干细胞（ASC）更丰富，更容易获得;此外，它们还具有强大的成骨能力。虽然这两种细胞类型被广泛认为非常相似，但人们越来越认识到它们在生物学和对生长因子的反应方面可能存在先天差异。特别是，报告表明，它们对血小板衍生生长因子BB（PDGF-BB）的成骨反应明显不同：MSC对PDGF-BB呈阴性反应或根本不反应，而ASC对生理浓度的PDGF-BB表现出增强的矿化反应。在这项研究中，我们直接测试了MSC和ASC对PDGF-BB的成骨反应之间是否存在根本差异。在相同的成骨条件下培养的MSC和ASC对20 ng/mL的PDGF-BB的反应一致：MSC在矿化方面没有表现出差异，而ASC每个细胞产生更多的钙。siRNA介导的ASC内PDGFRβ的敲低消除了它们对PDGF-BB的应答能力。基因表达也不同; MSC通常下调，ASC通常上调成骨基因以响应PDGF-BB。与对照ASC相比，转导ASC以产生PDGF-BB导致在临界尺寸的鼠颅骨缺损内更多的再生骨，表明PDGF-BB与ASC特异性结合使用可能增强骨再生的组织工程方法。
Tissue engineering using mesenchymal stem cells holds great promise for regenerating critically sized bone defects. While the bone marrow-derived mesenchymal stem cell (MSC) is the most widely studied stromal/stem cell type for this application, its rarity within bone marrow and painful isolation procedure have motivated investigation of alternative cell sources. Adipose-derived stromal/stem cells (ASCs) are more abundant and more easily procured; furthermore, they also possess robust osteogenic potency. While these two cell types are widely considered very similar, there is a growing appreciation of possible innate differences in their biology and response to growth factors. In particular, reports indicate that their osteogenic response to platelet-derived growth factor BB (PDGF-BB) is markedly different: MSCs responded negatively or not at all to PDGF-BB while ASCs exhibited enhanced mineralization in response to physiological concentrations of PDGF-BB. In this study, we directly tested whether a fundamental difference existed between the osteogenic responses of MSCs and ASCs to PDGF-BB. MSCs and ASCs cultured under identical osteogenic conditions responded disparately to 20 ng/mL of PDGF-BB: MSCs exhibited no difference in mineralization while ASCs produced more calcium per cell. siRNA-mediated knockdown of PDGFRβ within ASCs abolished their ability to respond to PDGF-BB. Gene expression was also different; MSCs generally downregulated and ASCs generally upregulated osteogenic genes in response to PDGF-BB. ASCs transduced to produce PDGF-BB resulted in more regenerated bone within a critically sized murine calvarial defect compared to control ASCs, indicating PDGF-BB used specifically in conjunction with ASCs might enhance tissue engineering approaches for bone regeneration.