Human-Induced Pluripotent Stem Cells (iPSCs) for Disease Modeling and Insulin Target Cell Regeneration in the Treatment of Insulin Resistance: A Review

Thiab, Sama; Azeez, Juberiya M.; Anala, Alekya; Nanda, Moksha; Khan, Somieya; Butler, Alexandra E.; Nandakumar, Manjula

doi:10.3390/cells14151188

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Open AccessReview

Human-Induced Pluripotent Stem Cells (iPSCs) for Disease Modeling and Insulin Target Cell Regeneration in the Treatment of Insulin Resistance: A Review

by

Sama Thiab

^†,

Juberiya M. Azeez

^†,

Alekya Anala

,

Moksha Nanda

,

Somieya Khan

,

Alexandra E. Butler

^*

and

Manjula Nandakumar

^*

Royal College of Surgeons in Ireland Bahrain, Busaiteen 15503, Bahrain

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Cells 2025, 14(15), 1188; https://doi.org/10.3390/cells14151188 (registering DOI)

Submission received: 23 June 2025 / Revised: 22 July 2025 / Accepted: 30 July 2025 / Published: 1 August 2025

(This article belongs to the Special Issue Advances in Human Pluripotent Stem Cells)

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Abstract

Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired pancreatic beta cell function and insulin resistance (IR) in peripheral organs, namely the liver, skeletal muscle, and adipose tissue. Additional insulin target tissues, including cardiomyocytes and neuronal cells, are also affected. The advent of stem cell research has opened new avenues for tackling this disease, particularly through the regeneration of insulin target cells and the establishment of disease models for further investigation. Human-induced pluripotent stem cells (iPSCs) have emerged as a valuable resource for generating specialized cell types, such as hepatocytes, myocytes, adipocytes, cardiomyocytes, and neuronal cells, with diverse applications ranging from drug screening to disease modeling and, importantly, treating IR in T2D. This review aims to elucidate the significant applications of iPSC-derived insulin target cells in studying the pathogenesis of insulin resistance and T2D. Furthermore, recent differentiation strategies, protocols, signaling pathways, growth factors, and advancements in this field of therapeutic research for each specific iPSC-derived cell type are discussed.

Keywords: human-induced pluripotent stem cells; insulin resistance; diabetes mellitus; iPSC-derived insulin target cells; iPSC differentiation

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MDPI and ACS Style

Thiab, S.; Azeez, J.M.; Anala, A.; Nanda, M.; Khan, S.; Butler, A.E.; Nandakumar, M. Human-Induced Pluripotent Stem Cells (iPSCs) for Disease Modeling and Insulin Target Cell Regeneration in the Treatment of Insulin Resistance: A Review. Cells 2025, 14, 1188. https://doi.org/10.3390/cells14151188

AMA Style

Thiab S, Azeez JM, Anala A, Nanda M, Khan S, Butler AE, Nandakumar M. Human-Induced Pluripotent Stem Cells (iPSCs) for Disease Modeling and Insulin Target Cell Regeneration in the Treatment of Insulin Resistance: A Review. Cells. 2025; 14(15):1188. https://doi.org/10.3390/cells14151188

Chicago/Turabian Style

Thiab, Sama, Juberiya M. Azeez, Alekya Anala, Moksha Nanda, Somieya Khan, Alexandra E. Butler, and Manjula Nandakumar. 2025. "Human-Induced Pluripotent Stem Cells (iPSCs) for Disease Modeling and Insulin Target Cell Regeneration in the Treatment of Insulin Resistance: A Review" Cells 14, no. 15: 1188. https://doi.org/10.3390/cells14151188

APA Style

Thiab, S., Azeez, J. M., Anala, A., Nanda, M., Khan, S., Butler, A. E., & Nandakumar, M. (2025). Human-Induced Pluripotent Stem Cells (iPSCs) for Disease Modeling and Insulin Target Cell Regeneration in the Treatment of Insulin Resistance: A Review. Cells, 14(15), 1188. https://doi.org/10.3390/cells14151188

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Human-Induced Pluripotent Stem Cells (iPSCs) for Disease Modeling and Insulin Target Cell Regeneration in the Treatment of Insulin Resistance: A Review

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