Restoration of sweat glands (SwGs) represents a great issue in patients with extensive skin defects. Recent methods combining organoid technology with cell fate reprogramming hold promise for developing new regenerative methods for SwG regeneration. Here, a practical strategy for engineering functional human SwGs in vitro and in vivo is provided. First, by forced expression of the ectodysplasin-A in human epidermal keratinocytes (HEKs) combined with specific SwG culture medium, HEKs are efficiently converted into SwG cells (iSwGCs). The iSwGCs show typical morphology, gene expression pattern, and functions resembling human primary SwG cells. Second, by culturing the iSwGCs in a special 3D culturing system, SwG organoids (iSwGOs) that exhibit structural and biological features characteristic of native SwGs are obtained. Finally, these iSwGOs are successfully transplanted into a mouse skin damage model and they develop into fully functioning SwGs in vivo. Regeneration of functional SwG organoids from reprogrammed HEKs highlights the great translational potential for personalized SwG regeneration in patients with large skin defects.

中文翻译：

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源自重编程表皮角质形成细胞的汗腺类器官在功能上概括了受损皮肤

汗腺 (SwGs) 的恢复对于患有广泛皮肤缺陷的患者来说是一个很大的问题。最近将类器官技术与细胞命运重编程相结合的方法有望开发用于 SwG 再生的新再生方法。在这里，提供了一种在体外和体内工程化功能性人类 SwG 的实用策略。首先，通过在人表皮角质形成细胞 (HEKs) 中强制表达 ectodysplasin-A 并结合特定的 SwG 培养基，HEKs 被有效地转化为 SwG 细胞 (iSwGCs)。iSwGC 显示出与人类原代 SwG 细胞相似的典型形态、基因表达模式和功能。其次，通过在特殊的 3D 培养系统中培养 iSwGC，获得了具有天然 SwG 的结构和生物学特征的 SwG 类器官 (iSwGO)。最后，这些 iSwGO 成功移植到小鼠皮肤损伤模型中，并在体内发育成功能齐全的 SwG。从重编程的 HEK 中再生功能性 SwG 类器官突出了大皮肤缺损患者个性化 SwG 再生的巨大转化潜力。