Self-organization of vascularized skeletal muscle from bovine embryonic stem cells.
Self-organization of vascularized skeletal muscle from bovine embryonic stem cells.
复制标题
来自牛胚胎干细胞的血管化骨骼肌的自组织。
DOI：
10.1101/2024.03.22.586252
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Ebisuya,Miki
中科院分区：
文献类型：
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作者：
Sanaki-Matsumiya,Marina;Villava,Casandra;Rappez,Luca;Haase,Kristina;Wu,Jun;Ebisuya,Miki
作为传统肉类的替代品，养殖牛肉具有很大的潜力。虽然成体干细胞通常被用作培养牛肉的细胞来源，但其增殖和分化能力有限。为了生产人工培养的牛排，目前的生产计划通常需要分别制备多种细胞类型，并通过复杂的工程将它们组装成结构化的组织。在这项研究中，我们提出并报道了从牛胚胎干细胞（ESCs）中共同诱导骨骼肌、神经元和内皮细胞以及在二维和三维培养中组织结构的自组织。以牛ESCs为材料，通过诱导体前中胚层（PSM）逐步诱导牛肌细胞。带肌瘤的肌肉纤维在15天内出现，显示钙振荡响应于共诱导的牛脊髓神经元的输入。牛内皮细胞也通过PSM共诱导，在组织内形成均匀的血管网络。我们的无血清、快速共诱导方案代表了具有综合血管和神经支配的自组织牛排的里程碑。
Cultured beef holds promising potential as an alternative to traditional meat options. While adult stem cells are commonly used as the cell source for cultured beef, their proliferation and differentiation capacities are limited. To produce cultured beef steaks, current manufacturing plans often require the separate preparation of multiple cell types and intricate engineering for assembling them into structured tissues. In this study, we propose and report the co-induction of skeletal muscle, neuronal, and endothelial cells from bovine embryonic stem cells (ESCs) and the self-organization of tissue structures in 2- and 3-dimensional cultures. Bovine myocytes were induced in a stepwise manner through the induction of presomitic mesoderm (PSM) from bovine ESCs. Muscle fibers with sarcomeres appeared within 15 days, displaying calcium oscillations responsive to inputs from co-induced bovine spinal neurons. Bovine endothelial cells were also co-induced via PSM, forming uniform vessel networks inside tissues. Our serum-free, rapid co-induction protocols represent a milestone toward self-organizing beef steaks with integrated vasculature and innervation.