Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin.

Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin.
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源自重新编程的表皮角质形成细胞的汗腺类器官功能性重现受损皮肤

DOI:
10.1002/advs.202103079
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发表时间:
2021-11
期刊:
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子:
--
通讯作者:
Fu X
Fu X
中科院分区:
其他
文献类型:
--
作者:
Sun X;Xiang J;Chen R;Geng Z;Wang L;Liu Y;Ji S;Chen H;Li Y;Zhang C;Liu P;Yue T;Dong L;Fu X

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汗腺(SwG)的恢复在具有广泛皮肤缺损的患者中是一个大问题。结合类器官技术与细胞命运重编程的最新方法有望为SwG再生开发新的再生方法。在这里,提供了一个实用的策略,在体外和体内工程功能的人SwGs。首先,通过在人表皮角质形成细胞(HEK)中强制表达外胚层发育不良蛋白-A与特异性SwG培养基组合,HEK被有效地转化为SwG细胞(iSwGC)。iSwGC显示出与人原代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,获得表现出天然SwG的结构和生物学特征的SwG类器官(iSwG)。最后,这些iSwG被成功地移植到小鼠皮肤损伤模型中,并且它们在体内发育成完全功能的SwG。从重编程的HEK再生功能性SwG类器官突出了在具有大皮肤缺损的患者中个性化SwG再生的巨大转化潜力。
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.
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