In vitro expanded skeletal myogenic progenitors from pluripotent stem cell-derived teratomas have high engraftment capacity.
In vitro expanded skeletal myogenic progenitors from pluripotent stem cell-derived teratomas have high engraftment capacity.
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DOI：
10.1016/j.stemcr.2021.10.014
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发表时间：
2021-12-14
影响因子：
5.9
通讯作者：
Chan SSK
中科院分区：
文献类型：
--
作者：
Xie N;Chu SN;Azzag K;Schultz CB;Peifer LN;Kyba M;Perlingeiro RCR;Chan SSK
实现基于细胞的治疗肌肉萎缩性疾病的一大挑战是难以获得具有治疗意义的量的可移植细胞。我们之前描述了一种通过畸胎瘤形成从多能干细胞产生具有出色移植性的骨骼肌原祖细胞的方法。在这里，我们证明这些细胞在体外功能上可扩展，同时保留其体内再生潜力。在培养 37 天内，畸胎瘤来源的骨骼肌源性祖细胞可扩增至十亿倍。与新分选的对应细胞类似，扩增的细胞表达 PAX7，并且能够在体外形成多核肌管。重要的是，这些细胞在体内保持高度再生。移植后，扩增的细胞形成新的 DYSTROPHIN+ 纤维，可重建高达 40% 的胫骨前肌体积，并重新填充肌肉干细胞池。因此，我们的研究证明了生产大量用于移植的可移植骨骼肌原细胞的可能性。来自 PSC 衍生畸胎瘤的骨骼肌源祖细胞可在体外扩增 扩增细胞为 PAX7+，能够分化为 MHC+ 肌管 扩增细胞植入并再生带有成体肌球蛋白和神经支配的纤维 扩增细胞在移植后重新填充肌肉干细胞生态位 在本文中，Chan 及其同事表明，从 PSC 衍生畸胎瘤中获得的骨骼肌源祖细胞可在培养物中扩增并保留高度再生。移植后，扩增的细胞牢固地移植形成新的肌肉纤维并重建肌肉干细胞库。这项研究是为下游应用产生大量可移植骨骼肌原祖细胞的一个进步。
One major challenge in realizing cell-based therapy for treating muscle-wasting disorders is the difficulty in obtaining therapeutically meaningful amounts of engraftable cells. We have previously described a method to generate skeletal myogenic progenitors with exceptional engraftability from pluripotent stem cells via teratoma formation. Here, we show that these cells are functionally expandable in vitro while retaining their in vivo regenerative potential. Within 37 days in culture, teratoma-derived skeletal myogenic progenitors were expandable to a billion-fold. Similar to their freshly sorted counterparts, the expanded cells expressed PAX7 and were capable of forming multinucleated myotubes in vitro. Importantly, these cells remained highly regenerative in vivo. Upon transplantation, the expanded cells formed new DYSTROPHIN+ fibers that reconstituted up to 40% of tibialis anterior muscle volume and repopulated the muscle stem cell pool. Our study thereby demonstrates the possibility of producing large quantities of engraftable skeletal myogenic cells for transplantation. Skeletal myogenic progenitors from PSC-derived teratomas are expandable in vitro Expanded cells are PAX7+ and are capable of differentiating into MHC+ myotubes Expanded cells engraft and regenerate fibers with adult myosins and innervation Expanded cells repopulate the muscle stem cell niche after transplantation In this article, Chan and colleagues show that skeletal myogenic progenitors obtained from PSC-derived teratomas are expandable in cultures and remain highly regenerative. Upon transplantation, the expanded cells robustly engraft to form new muscle fibers and reconstitute the muscle stem cell pool. This study is an advance toward generating large quantities of engraftable skeletal myogenic progenitors for downstream applications.
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