Ectopic transient overexpression of OCT-4 facilitates BMP4-induced osteogenic transdifferentiation of human umbilical vein endothelial cells
Ectopic transient overexpression of OCT-4 facilitates BMP4-induced osteogenic transdifferentiation of human umbilical vein endothelial cells
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DOI：
10.1177/2041731420909208
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发表时间：
2020-03-01
影响因子：
8.2
通讯作者：
Hwang, Nathaniel S.
中科院分区：
文献类型：
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作者：
Kim, Seung Hyun L.;Lee, Seunghun S.;Hwang, Nathaniel S.
限制自体细胞治疗的细胞来源已成为干细胞治疗和组织工程领域的最新研究热点。在众多的研究进展中，直接转化或转分化是一种值得注意和可行的产生和获得想要的细胞源的策略。到目前为止，细胞转分化技术在组织工程中的应用主要局限于从多种细胞类型中高效地获得单一的需要细胞类型。然而，完整组织的再生总是需要多种细胞类型，这构成了固有的复杂性。在这项研究中，通过瞬时异位表达八聚体结合转录因子4(oct-4)基因和骨形态发生蛋白4处理人脐静脉内皮细胞来促进成骨分化。与单独应用骨形态发生蛋白4相比，OCT-4联合骨形态发生蛋白4治疗可增强成骨标志物如核心结合因子α1、碱性磷酸酶和胶原1的表达。此外，我们还将明胶-肝素冷冻凝胶应用于颅骨缺损模型中，用于体内骨形成。体内标本的显微计算机断层扫描和组织学分析表明，OCT-4转染组和骨形态发生蛋白4组均能有效地将内皮细胞转分化为成骨细胞。提示OCT-4和骨形态发生蛋白4联合作用于内皮细胞是一种可靠的多细胞转分化模型，可应用于骨组织工程。
Limitation in cell sources for autologous cell therapy has been a recent focus in stem cell therapy and tissue engineering. Among various research advances, direct conversion, or transdifferentiation, is a notable and feasible strategy for the generation and acquirement of wanted cell source. So far, utilizing cell transdifferentiation technology in tissue engineering was mainly restricted at achieving single wanted cell type from diverse cell types with high efficiency. However, regeneration of a complete tissue always requires multiple cell types which poses an intrinsic complexity. In this study, enhanced osteogenic differentiation was achieved by transient ectopic expression of octamer-binding transcription factor 4 (OCT-4) gene followed by bone morphogenetic protein 4 treatment on human umbilical vein endothelial cells. OCT-4 transfection and bone morphogenetic protein 4 treatment resulted in enhanced expression of osteogenic markers such as core-binding factor alpha 1, alkaline phosphatase, and collagen 1 compared with bone morphogenetic protein 4 treatment alone. Furthermore, we employed gelatin-heparin cryogel in cranial defect model for in vivo bone formation. Micro-computed tomography and histological analysis of in vivo samples showed that OCT-4 transfection followed by bone morphogenetic protein 4 treatment resulted in efficient transdifferentiation of endothelial cells to osteogenic cells. These results suggest that the combination of OCT-4 and bone morphogenetic protein 4 on endothelial cells would be a reliable multicellular transdifferentiation model which could be applied for bone tissue engineering.