Application of human iPSC-derived white, beige, and brown adipocytes for metabolic disease modeling and transplantation therapy.

IF 3.2 4区医学 Q3 CELL & TISSUE ENGINEERING

Cell Transplantation Pub Date : 2025-01-01 Epub Date: 2025-06-19 DOI:10.1177/09636897251346599

Yamato Keidai, Junji Fujikura, Daisuke Yabe

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Abstract

Adipocyte dysfunction plays a critical role in the pathogenesis of metabolic diseases, including type 2 diabetes (T2D). Human induced pluripotent stem cells (hiPSCs) offer a powerful platform for generating white, beige, and brown adipocytes, supporting both disease modeling and therapeutic research. This review provides a comprehensive summary of current differentiation methods to produce three functionally mature adipocyte types from pluripotent stem cells (PSCs), including forced gene expression techniques, developmental biology-inspired approaches, and advanced three-dimensional (3D) culture systems that enhance cellular maturity and functional relevance. PSC-derived white adipocytes contribute to modeling adipocyte dysfunction not only in conditions such as insulin resistance, lipodystrophy, and premature aging but also in more complex metabolic diseases, including T2D, facilitating the investigation of disease mechanisms and the identification of novel therapeutic targets. In addition, iPSC-based models provide a robust platform for exploring genetic regulation by genome-wide association studies (GWAS)-identified variants through population genetics. This review also evaluates the therapeutic potential of iPSC-derived white, beige, and brown adipocytes in cell transplantation therapy for metabolic diseases, with a focus on engraftment potential and metabolic improvement. Enhancing the maturity and subtype specificity of PSC-derived adipocytes is expected to accelerate the development of personalized medicine and innovative therapeutic strategies for metabolic diseases.

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人类ipsc衍生的白色、米色和棕色脂肪细胞在代谢疾病建模和移植治疗中的应用

脂肪细胞功能障碍在代谢性疾病，包括2型糖尿病（T2D）的发病机制中起着关键作用。人类诱导多能干细胞（hipsc）为生成白色、米色和棕色脂肪细胞提供了一个强大的平台，支持疾病建模和治疗研究。本文综述了目前从多能干细胞（PSCs）中产生三种功能成熟的脂肪细胞类型的分化方法，包括强制基因表达技术、发育生物学启发方法和先进的三维（3D）培养系统，以提高细胞成熟度和功能相关性。psc衍生的白色脂肪细胞不仅在胰岛素抵抗、脂肪营养不良和早衰等情况下有助于模拟脂肪细胞功能障碍，而且在包括T2D在内的更复杂的代谢疾病中也有助于研究疾病机制和确定新的治疗靶点。此外，基于ipsc的模型为通过群体遗传学探索全基因组关联研究（GWAS）鉴定的变异的遗传调控提供了一个强大的平台。本综述还评估了ipsc来源的白色、米色和棕色脂肪细胞在代谢性疾病的细胞移植治疗中的治疗潜力，重点是移植潜力和代谢改善。提高psc来源脂肪细胞的成熟度和亚型特异性有望加速代谢性疾病的个性化医疗和创新治疗策略的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Transplantation 生物-细胞与组织工程

CiteScore

6.00

自引率

3.00%

发文量

审稿时长

6 months

期刊介绍： Cell Transplantation, The Regenerative Medicine Journal is an open access, peer reviewed journal that is published 12 times annually. Cell Transplantation is a multi-disciplinary forum for publication of articles on cell transplantation and its applications to human diseases. Articles focus on a myriad of topics including the physiological, medical, pre-clinical, tissue engineering, stem cell, and device-oriented aspects of the nervous, endocrine, cardiovascular, and endothelial systems, as well as genetically engineered cells. Cell Transplantation also reports on relevant technological advances, clinical studies, and regulatory considerations related to the implantation of cells into the body in order to provide complete coverage of the field.