用于心力衰竭建模和修复的高级成熟的人体肌肉
Malte Tiburcy1, James E Hudson1, Paul Balfanz1
1From Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Germany (M.T., J.E.H., P.B., S.S., T.M., M.-L.C.L., E.L., F.R., S.Z., E. Wettwer, W.-H.Z.); German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany (M.T., J.E.H., P.B., S.S., T.M., M.-L.C.L., E.L., F.R., S.Z., E. Wingender, W.A.L., W.-H.Z.); Institute of Bioinformatics, University Medical Center Göttingen, Germany (S.Z., E. Wingender); Stanford Cardiovascular Institute (J.R., M.W., J.D.G., J.C.W.) and Department of Radiology (J.D.G., J.C.W.), Molecular Imaging Program, Stanford University School of Medicine, CA; The Sohnis Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Technion-Israel Institute of Technology, Haifa (I.K., L.G.); Institute of Pharmacology and Toxicology, Technical University Dresden, Germany (E. Wettwer, U.R.); University Medical Center Utrecht and Hubrecht Institute, The Netherlands (P.D., L.W.v.L.); Leiden University Medical Center, The Netherlands (M.J.G.); Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Germany (S.K., K.T., G.H., W.A.L.); Center for Applied Technology, Beckman Research Institute, City of Hope, Duarte, CA (L.A.C.); Department of Cardiovascular Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, Germany (A.U., W.A.L.); New Laura and Isaac Perlmutter Cancer Center at New York University Langone (T.A., B.N.); and McEwen Centre for Regenerative Medicine, Toronto, Canada (G.K.). The current address for Dr Hudson is Laboratory for Cardiac Regeneration, School of Biomedical Sciences, The University of Queensland, Australia.
这项研究从干细胞开发了人工人心肌 (EHM),实现了心脏修复和疾病建模的成人功能. 这种可扩展的EHM技术对临床应用具有前景.
科学领域:
- 心血管工程
- 干细胞生物学
- 复原医学
背景情况:
- 来自干细胞的心肌细胞需要进一步成熟才能在心脏应用中有效使用.
- 目前的方法在达到成年人的结构和功能性质方面面临挑战.
研究的目的:
- 促进干细胞衍生的心肌细胞在人工人心肌 (EHM) 中的成熟.
- 在定义的无血清条件下,在EHM中获得成人类型的表型.
主要方法:
- 对EHM生成的细胞组成,基质和介质进行系统的研究.
- 使用胚胎和诱导多能干细胞衍生的心肌细胞和纤维细胞.
- 使用形态,功能和转录组分析来评估成熟度.
主要成果:
- EHM表现出产后心肌的结构和功能特性,包括棒状心肌细胞,显著的收缩力和正力频率响应.
- 证明了常规的β-上腺素信号和对甲醇胺毒性的反应,模仿了心力衰竭的标志.
- 展示了EHM对潜在的临床心脏修复需求的可扩展性.
结论:
- 一种普遍适用的技术的概念验证,用于大规模设计人类心肌.
- 在定义的无血清条件下从干细胞获得的EHM适用于疾病建模和心脏修复.
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