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从人多能干细胞中生成功能性和高增殖性黑素细胞:治疗皮肤色素沉着紊乱的生物治疗方法的有前途的工具。

Generating Functional and Highly Proliferative Melanocytes Derived from Human Pluripotent Stem Cells: A Promising Tool for Biotherapeutic Approaches to Treat Skin Pigmentation Disorders.

机构信息

Centre d'Etude des Cellules Souches, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, French Muscular Disease Association, 91100 Corbeil-Essonnes, France.

Centre d'Etude des Cellules Souches, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, Cell Biology Platform, Research and Technological Innovation Team, 91100 Corbeil-Essonnes, France.

出版信息

Int J Mol Sci. 2023 Mar 29;24(7):6398. doi: 10.3390/ijms24076398.

Abstract

Melanocytes are essential for skin homeostasis and protection, and their loss or misfunction leads to a wide spectrum of diseases. Cell therapy utilizing autologous melanocytes has been used for years as an adjunct treatment for hypopigmentary disorders such as vitiligo. However, these approaches are hindered by the poor proliferative capacity of melanocytes obtained from skin biopsies. Recent advances in the field of human pluripotent stem cells have fueled the prospect of generating melanocytes. Here, we have developed a well-characterized method to produce a pure and homogenous population of functional and proliferative melanocytes. The genetic stability and potential transformation of melanocytes from pluripotent stem cells have been evaluated over time during the in vitro culture process. Thanks to transcriptomic analysis, the molecular signatures all along the differentiation protocol have been characterized, providing a solid basis for standardizing the protocol. Altogether, our results promise meaningful, broadly applicable, and longer-lasting advances for pigmentation disorders and open perspectives for innovative biotherapies for pigment disorders.

摘要

黑素细胞对于皮肤的稳态和保护至关重要,其丧失或功能障碍会导致广泛的疾病。利用自体黑素细胞的细胞疗法多年来一直被用作治疗色素减退性疾病(如白癜风)的辅助治疗方法。然而,这些方法受到从皮肤活检中获得的黑素细胞增殖能力差的限制。人类多能干细胞领域的最新进展激发了产生黑素细胞的前景。在这里,我们开发了一种经过充分表征的方法,可以产生纯且同质的功能和增殖性黑素细胞群体。在体外培养过程中,随着时间的推移,评估了多能干细胞来源的黑素细胞的遗传稳定性和潜在转化。转录组分析的结果,沿分化方案的分子特征得到了表征,为标准化方案提供了坚实的基础。总之,我们的结果有望为色素紊乱带来有意义的、广泛适用的和更持久的进展,并为色素紊乱的创新生物疗法开辟新的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9673/10094141/71d6460f7671/ijms-24-06398-g001.jpg

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