Core-shell hydrogel microfiber-expanded pluripotent stem cell-derived lung progenitors applicable to lung reconstruction in vivo
Core-shell hydrogel microfiber-expanded pluripotent stem cell-derived lung progenitors applicable to lung reconstruction in vivo
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DOI：
10.1016/j.biomaterials.2021.121031
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发表时间：
2021-07-23
期刊：
影响因子：
14
通讯作者：
Gotoh, Shimpei
中科院分区：
文献类型：
--
作者：
Ikeo, Satoshi;Yamamoto, Yuki;Gotoh, Shimpei
肺移植是治疗终末期肺部疾病的唯一方法;然而，供体短缺是一个全球性问题。利用人多能干细胞（hPSC）进行器官再生是一种很有前途的方法。然而，尚未报道用于移植目的的分离的hPSC衍生的肺祖细胞（hLP）的扩增方法。在此，我们建立了一个扩增系统的基础上，他们的三维培养的核-壳水凝胶微纤维，确保其维持分化为肺泡和气道上皮细胞，包括肺泡II型（AT 2）细胞的双能性。此外，我们开发了一种有效的体内移植方法，使用内窥镜辅助经气管给药系统;成功的植入和体内分化的hLP到肺泡上皮细胞（纳入肺泡）进行了观察。重要的是，在微纤维的背景下扩增的hLP成功地移植到鼠肺中，为基于细胞的肺部疾病治疗开辟了途径。因此，我们的新方法具有潜在的再生医学应用;此外，通过基于微纤维的技术产生的高质量hLP和AT 2细胞对于药物发现目的是有价值的。
Lung transplantation is the only treatment available for end-stage lung diseases; however, donor shortage is a global issue. The use of human pluripotent stem cells (hPSCs) for organ regeneration is a promising approach. Nevertheless, methods for the expansion of isolated hPSC-derived lung progenitors (hLPs) for transplantation purposes have not yet been reported. Herein, we established an expansion system of hLPs based on their threedimensional culture in core-shell hydrogel microfibers, that ensures the maintenance of their bipotency for differentiation into alveolar and airway epithelial cells including alveolar type II (AT2) cells. Further, we developed an efficient in vivo transplantation method using an endoscope-assisted transtracheal administration system; the successful engraftment and in vivo differentiation of hLPs into alveolar epithelial cells (incorporated into the alveoli) was observed. Importantly, expanded hLPs in the context of microfibers were successfully transplanted into the murine lungs, opening avenues for cell-based therapies of lung diseases. Therefore, our novel method has potential regenerative medicine applications; additionally, the high-quality hLPs and AT2 cells generated via the microfiber-based technology are valuable for drug discovery purposes.