人多能干细胞有效分化为能够长期稳定分泌睾酮的leydigi样细胞。

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING
Katsuya Sato, Michiyo Koyanagi-Aoi, Keiichiro Uehara, Yosuke Yamashita, Masakazu Shinohara, Suji Lee, Anika Reinhardt, Knut Woltjen, Koji Chiba, Hideaki Miyake, Masato Fujisawa, Takashi Aoi
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引用次数: 0

摘要

迟发性性腺功能减退(LOH)综合征的特征是与年龄相关的睾酮缺乏,并对老年男性的生活质量产生负面影响。一种很有前景的治疗LOH综合征的方法是移植来自人类诱导多能干细胞(hiPSCs)的产生睾酮的leydigi样细胞(LLCs)。然而,先前的研究遇到了障碍,如细胞寿命有限,睾酮分泌不足,分化效率低。为了解决这些问题,我们开发了一种新的方案,包括强制NR5A1表达,促进中胚层分化的细胞因子鸡尾酒,以及从3D到2D培养的过渡。所得到的细胞在培养皿中存活超过16周,产生的睾酮是传统方法的22倍,构成了一个均匀的LLCs群体,未经纯化的分化效率超过99%。此外,这些llc被成功地皮下移植到小鼠体内,导致血清睾酮水平升高。我们的研究将促进LOH综合征的创新治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Efficient differentiation of human iPSCs into Leydig-like cells capable of long-term stable secretion of testosterone.

Late-onset hypogonadism (LOH) syndrome is characterized by age-related testosterone deficiency and negatively affects the quality of life of older men. A promising therapeutic approach for LOH syndrome is transplantation of testosterone-producing Leydig-like cells (LLCs) derived from human induced pluripotent stem cells (hiPSCs). However, previous studies have encountered obstacles, such as limited cell longevity, insufficient testosterone production, and inefficiency of differentiation. To address these issues, we developed a novel protocol that includes forced NR5A1 expression, a cytokine cocktail promoting mesoderm differentiation, and a transitional shift from 3D to 2D cultures. The resultant cells survived on culture dishes for over 16 weeks, produced 22-fold more testosterone than the conventional method, and constituted a homogeneous population of LLCs with a differentiation efficiency exceeding 99% without purification. Furthermore, these LLCs were successfully engrafted subcutaneously into mice, resulting in increased serum testosterone levels. Our study will facilitate innovative therapeutic strategies for LOH syndrome.

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来源期刊
Stem Cell Reports
Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
10.50
自引率
1.70%
发文量
200
审稿时长
28 weeks
期刊介绍: Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
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