Translational Cardiomyology, Department of Development and Regeneration, KU Leuven, 3000, Leuven, Belgium.
Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging, KU Leuven, 3000, Leuven, Belgium.
Nat Commun. 2017 Nov 1;8(1):1249. doi: 10.1038/s41467-017-01359-w.
Muscular dystrophies (MDs) are often characterized by impairment of both skeletal and cardiac muscle. Regenerative strategies for both compartments therefore constitute a therapeutic avenue. Mesodermal iPSC-derived progenitors (MiPs) can regenerate both striated muscle types simultaneously in mice. Importantly, MiP myogenic propensity is influenced by somatic lineage retention. However, it is still unknown whether human MiPs have in vivo potential. Furthermore, methods to enhance the intrinsic myogenic properties of MiPs are likely needed, given the scope and need to correct large amounts of muscle in the MDs. Here, we document that human MiPs can successfully engraft into the skeletal muscle and hearts of dystrophic mice. Utilizing non-invasive live imaging and selectively induced apoptosis, we report evidence of striated muscle regeneration in vivo in mice by human MiPs. Finally, combining RNA-seq and miRNA-seq data, we define miRNA cocktails that promote the myogenic potential of human MiPs.
肌肉萎缩症（MDs）通常表现为骨骼肌和心肌功能障碍。因此，针对这两个部位的再生策略是一种治疗途径。中胚层诱导多能干细胞衍生的祖细胞（MiPs）可以在小鼠中同时再生两种横纹肌。重要的是，MiP 的成肌倾向受体细胞谱系保留的影响。然而，目前尚不清楚人类 MiPs 是否具有体内潜能。此外，鉴于需要纠正 MD 中大量的肌肉，很可能需要增强 MiPs 内在成肌特性的方法。在这里，我们记录了人类 MiPs 可以成功植入到肌肉萎缩症小鼠的骨骼肌和心脏中。利用非侵入性活体成像和选择性诱导细胞凋亡，我们报告了人类 MiPs 在体内诱导横纹肌再生的证据。最后，结合 RNA-seq 和 miRNA-seq 数据，我们确定了 miRNA 鸡尾酒，可促进人类 MiPs 的成肌潜能。
