BMP10载药纳米基质支架: iPS源性心肌细胞的促熟新策略及其机制研究

iPS源性心肌细胞不成熟限制了iPS细胞在心肌再生治疗中的应用，亟待新的促熟策略。我们在上一基金中发现这种不成熟性直接影响组织工程心肌的功能重建，为此探索其促熟新策略与机制尤为迫切和重要！文献回顾及前期研究表明：ECM与促熟因子是调控心肌细胞成熟的关键因素，而BMP10是其潜在的促熟新因子。延伸前期研究基础，本研究拟利用已建立的αMHC-eGFP-iPS细胞系及心肌分化诱导体系，联合静电纺丝与纳米载药技术制备BMP10载药纳米基质支架，探讨拟生ECM微环境联合促熟因子BMP10的策略对iPS源性心肌细胞的促熟作用；结合抑制剂与阻断性抗体研究生物力学刺激下MEK-ERK1/2通路对心肌细胞结构与电生理成熟的调控作用，以阐明BMP10载药纳米基质支架影响iPS源性心肌细胞成熟的机制。预期研究成果有望建立一种有效促熟策略和阐明心肌细胞的成熟新机制，为iPS细胞更好地应用于心肌再生治疗奠定基础。

The immaturity of iPS-derived cardiomyocytes (iPS-CM) seriously limits its application in myocardial regeneration therapy, and new strategies for promoting maturation of iPS-CM are urgent to be explored. In our previous fund, we found that the immaturity of iPS-CM directly affected the functional reconstruction of tissue-engineered myocardium. Therefore, it is particularly urgent and important to explore new strategies and its mechanism for promoting maturation of iPS-CM. Literature review and our previous research indicates that ECM and pro-maturity factor are key regulatory factors for maturation of cardiomyocytes, and BMP10 is a new potential factor. Based on previous research, this study is explored to prepared BMP10 drug-loaded nanometer matrix scaffold by combination of electrospinning and drug-loaded technology. Using previously established αMHC-eGFP-iPS cell lines and cardiomyocytes differentiation system, we explore the role of biomimetic ECM microenvironment and BMP10 on maturation of iPS-CM. By using inhibitors and blocking antibodies, this study try to reveal the regulatory role of MEK-ERK1/2 pathway mediated by biomechanical stimulation on structural and electrophysiological maturity of cardiomyocytes, thus to clarify the regulatory mechanisms of BMP10 drug-loaded nanometer matrix scaffold on the maturation of iPS-CM. The anticipated results are expected to establish an effective strategy to promote the maturation of iPS-CM and clarify its new mechanism, which will lay foundation for better application of iPS cells in myocardial regeneration therapy.