Evaluating iPSC-based interventions for diabetes: a systematic review and meta-analysis.
Diabetes mellitus (DM) is characterized by progressive β-cell dysfunction, and current therapies improve glycemic control without restoring endogenous β-cell mass. Induced pluripotent stem cell (iPSC)-based approaches offer a potential regenerative strategy. This systematic review and meta-analysis evaluates the efficacy and safety of iPSC-based interventions for diabetes in preclinical models.
A comprehensive literature search was conducted in PubMed, ScienceDirect, and Web of Science for studies published up to November 2025. Studies assessing iPSC-based therapies in diabetic models were systematically reviewed and quantitatively synthesized.
Thirty-one preclinical studies involving 424 animals were included. iPSC-based interventions were associated with reduced mortality (odds ratio [OR] 0.14) and reductions in blood glucose across 21 studies (mean difference [MD] -267.36). Glucose-lowering effects were observed under fasting, non-fasting, and glucose-challenge conditions and were accompanied by increased insulin and C-peptide levels. Improvements were also reported in several diabetes-related complications, including cardiac dysfunction, impaired wound healing, neuropathy, and retinopathy.
iPSC-based therapies show potential to improve glycemic control and diabetes-related complications in preclinical models, likely through a combination of endocrine replacement and paracrine-mediated regenerative mechanisms. However, substantial heterogeneity across outcome assessments, reliance on short- to mid-term follow-up, and limitations of experimental disease models constrain the interpretation and generalizability of these findings. Immune compatibility, long-term safety, and scalable manufacturing remain key challenges for clinical translation.
A comprehensive literature search was conducted in PubMed, ScienceDirect, and Web of Science for studies published up to November 2025. Studies assessing iPSC-based therapies in diabetic models were systematically reviewed and quantitatively synthesized.
Thirty-one preclinical studies involving 424 animals were included. iPSC-based interventions were associated with reduced mortality (odds ratio [OR] 0.14) and reductions in blood glucose across 21 studies (mean difference [MD] -267.36). Glucose-lowering effects were observed under fasting, non-fasting, and glucose-challenge conditions and were accompanied by increased insulin and C-peptide levels. Improvements were also reported in several diabetes-related complications, including cardiac dysfunction, impaired wound healing, neuropathy, and retinopathy.
iPSC-based therapies show potential to improve glycemic control and diabetes-related complications in preclinical models, likely through a combination of endocrine replacement and paracrine-mediated regenerative mechanisms. However, substantial heterogeneity across outcome assessments, reliance on short- to mid-term follow-up, and limitations of experimental disease models constrain the interpretation and generalizability of these findings. Immune compatibility, long-term safety, and scalable manufacturing remain key challenges for clinical translation.
Authors
Tan Tan, Anh Anh, Hien Hien, Trang Trang, Nguyet Nguyet, Linh Linh, Yen Yen, Quan Quan
View on Pubmed