Reprogramming of human fibroblasts into osteoblasts by insulin-like growth factor-binding protein 7.,STEM CELLS Translational Medicine

当前位置： X-MOL 学术 › Stem Cells Transl. Med. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Reprogramming of human fibroblasts into osteoblasts by insulin-like growth factor-binding protein 7.
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2020-01-06 , DOI: 10.1002/sctm.19-0281
ZuFu Lu _{1,

2} , Joyce Chiu ₃ , Lucinda R Lee _{4,

5} , Aaron Schindeler _{4,

5} , Miriam Jackson ₁ , Yogambha Ramaswamy _{1,

2} , Colin R Dunstan _{1,

2} , Philip J Hogg ₃ , Hala Zreiqat _{1,

2}

Affiliation

The induced pluripotent stem cell (iPSC) is a promising cell source for tissue regeneration. However, the therapeutic value of iPSC technology is limited due to the complexity of induction protocols and potential risks of teratoma formation. A trans‐differentiation approach employing natural factors may allow better control over reprogramming and improved safety. We report here a novel approach to drive trans‐differentiation of human fibroblasts into functional osteoblasts using insulin‐like growth factor binding protein 7 (IGFBP7). We initially determined that media conditioned by human osteoblasts can induce reprogramming of human fibroblasts to functional osteoblasts. Proteomic analysis identified IGFBP7 as being significantly elevated in media conditioned with osteoblasts compared with those with fibroblasts. Recombinant IGFBP7 induced a phenotypic switch from fibroblasts to osteoblasts. The switch was associated with senescence and dependent on autocrine IL‐6 signaling. Our study supports a novel strategy for regenerating bone by using IGFBP7 to trans‐differentiate fibroblasts to osteoblasts.

中文翻译：

通过胰岛素样生长因子结合蛋白 7 将人成纤维细胞重编程为成骨细胞。

诱导多能干细胞（iPSC）是一种有前景的组织再生细胞来源。然而，由于诱导方案的复杂性和畸胎瘤形成的潜在风险，iPSC 技术的治疗价值受到限制。利用自然因素的转分化方法可以更好地控制重编程并提高安全性。我们在此报告了一种使用胰岛素样生长因子结合蛋白 7 (IGFBP7) 驱动人类成纤维细胞转分化为功能性成骨细胞的新方法。我们最初确定，由人成骨细胞调节的培养基可以诱导人成纤维细胞重编程为功能性成骨细胞。蛋白质组学分析发现，与成纤维细胞相比，在成骨细胞条件培养基中 IGFBP7 显着升高。重组 IGFBP7 诱导从成纤维细胞到成骨细胞的表型转变。该开关与衰老相关，并依赖于自分泌 IL-6 信号传导。我们的研究支持了一种通过使用 IGFBP7 将成纤维细胞转分化为成骨细胞来再生骨的新策略。

更新日期：2020-01-06

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11