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

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Yamato Keidai, Junji Fujikura, Daisuke Yabe
Format: Article
Language:English
Published: SAGE Publishing 2025-06-01
Series:Cell Transplantation
Online Access:https://doi.org/10.1177/09636897251346599
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850217765013553152
author Yamato Keidai
Junji Fujikura
Daisuke Yabe
author_facet Yamato Keidai
Junji Fujikura
Daisuke Yabe
author_sort Yamato Keidai
collection DOAJ
description 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.
format Article
id doaj-art-c1ca0d32e604441b8e18cfc671cae422
institution OA Journals
issn 1555-3892
language English
publishDate 2025-06-01
publisher SAGE Publishing
record_format Article
series Cell Transplantation
spelling doaj-art-c1ca0d32e604441b8e18cfc671cae4222025-08-20T02:07:59ZengSAGE PublishingCell Transplantation1555-38922025-06-013410.1177/09636897251346599Application of human iPSC-derived white, beige, and brown adipocytes for metabolic disease modeling and transplantation therapyYamato Keidai0Junji Fujikura1Daisuke Yabe2Department of Diabetes and Endocrinology, Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai, Osaka, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanCenter for One Medicine Innovative Translational Research, Gifu University Institute for Advanced Studies, Gifu, JapanAdipocyte 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.https://doi.org/10.1177/09636897251346599
spellingShingle Yamato Keidai
Junji Fujikura
Daisuke Yabe
Application of human iPSC-derived white, beige, and brown adipocytes for metabolic disease modeling and transplantation therapy
Cell Transplantation
title Application of human iPSC-derived white, beige, and brown adipocytes for metabolic disease modeling and transplantation therapy
title_full Application of human iPSC-derived white, beige, and brown adipocytes for metabolic disease modeling and transplantation therapy
title_fullStr Application of human iPSC-derived white, beige, and brown adipocytes for metabolic disease modeling and transplantation therapy
title_full_unstemmed Application of human iPSC-derived white, beige, and brown adipocytes for metabolic disease modeling and transplantation therapy
title_short Application of human iPSC-derived white, beige, and brown adipocytes for metabolic disease modeling and transplantation therapy
title_sort application of human ipsc derived white beige and brown adipocytes for metabolic disease modeling and transplantation therapy
url https://doi.org/10.1177/09636897251346599
work_keys_str_mv AT yamatokeidai applicationofhumanipscderivedwhitebeigeandbrownadipocytesformetabolicdiseasemodelingandtransplantationtherapy
AT junjifujikura applicationofhumanipscderivedwhitebeigeandbrownadipocytesformetabolicdiseasemodelingandtransplantationtherapy
AT daisukeyabe applicationofhumanipscderivedwhitebeigeandbrownadipocytesformetabolicdiseasemodelingandtransplantationtherapy