Hypoxia facilitates proliferation of smooth muscle cells derived from pluripotent stem cells for vascular tissue engineering

IF 3.1 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Tissue Engineering and Regenerative Medicine Pub Date : 2022-05-28 DOI:10.1002/term.3324
Lijun Fang, Jingyi Mei, Boqian Yao, Jiang Liu, Peng Liu, Xichun Wang, Jiahui Zhou, Zhanyi Lin
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引用次数: 1

Abstract

Tissue-engineered blood vessels (TEBVs) show significant therapeutic potential for replacing diseased blood vessels. Vascular smooth muscle cells (VSMCs) derived from human induced pluripotent stem cells (hiPSCs) via embryoid body (EB)-based differentiation, are promising seed cells to construct TEBVs. However, obtaining sufficient high-quality hiPSC-VSMCs remains challenging. Stem cells are located in a niche characterized by hypoxia. Hence, we explored molecular and cellular functions at different induction stages from the EB formation commencement to the end of directed differentiation under normoxic and hypoxic conditions, respectively. Hypoxia enhanced the formation, adhesion and amplification rates of EBs. During directed differentiation, hiPSC-VSMCs exhibited increased cell viability under hypoxic conditions. Moreover, seeding hypoxia-pretreated cells on biodegradable scaffolds, facilitated collagen I and elastin secretion, which has significant application value for TEBV development. Hence, we proposed that hypoxic treatment during differentiation effectively induces proliferative hiPSC-VSMCs, expanding high-quality seed cell sources for TEBV construction.

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缺氧有利于血管组织工程中多能干细胞衍生的平滑肌细胞的增殖
组织工程血管(TEBVs)在替代病变血管方面显示出显著的治疗潜力。血管平滑肌细胞(VSMCs)是由人诱导多能干细胞(hiPSCs)通过胚状体(EB)分化而来,是一种很有前途的构建TEBVs的种子细胞。然而,获得足够的高质量hipsc - vsmc仍然具有挑战性。干细胞处于一个以缺氧为特征的生态位。因此,我们分别在常氧和缺氧条件下探索了从EB形成开始到定向分化结束的不同诱导阶段的分子和细胞功能。缺氧可增强EBs的形成、粘附和扩增率。在定向分化过程中,hiPSC-VSMCs在缺氧条件下表现出更高的细胞活力。此外,将缺氧预处理的细胞植入生物可降解支架上,促进胶原I和弹性蛋白的分泌,对TEBV的发育具有重要的应用价值。因此,我们提出在分化过程中缺氧处理可有效诱导增殖的hiPSC-VSMCs,为TEBV的构建扩大高质量的种子细胞来源。
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来源期刊
CiteScore
7.50
自引率
3.00%
发文量
97
审稿时长
4-8 weeks
期刊介绍: Journal of Tissue Engineering and Regenerative Medicine publishes rapidly and rigorously peer-reviewed research papers, reviews, clinical case reports, perspectives, and short communications on topics relevant to the development of therapeutic approaches which combine stem or progenitor cells, biomaterials and scaffolds, growth factors and other bioactive agents, and their respective constructs. All papers should deal with research that has a direct or potential impact on the development of novel clinical approaches for the regeneration or repair of tissues and organs. The journal is multidisciplinary, covering the combination of the principles of life sciences and engineering in efforts to advance medicine and clinical strategies. The journal focuses on the use of cells, materials, and biochemical/mechanical factors in the development of biological functional substitutes that restore, maintain, or improve tissue or organ function. The journal publishes research on any tissue or organ and covers all key aspects of the field, including the development of new biomaterials and processing of scaffolds; the use of different types of cells (mainly stem and progenitor cells) and their culture in specific bioreactors; studies in relevant animal models; and clinical trials in human patients performed under strict regulatory and ethical frameworks. Manuscripts describing the use of advanced methods for the characterization of engineered tissues are also of special interest to the journal readership.
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