Volume 16, Issue 62 (5-2026)
NCMBJ 2026, 16(62): 1-22 |
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Heydari S F, Moosazadeh Moghaddam M, Sari S, Heiat M. A review of diabetes treatment using mesenchymal stem cells and the role of chemical and physical factors in the differentiation process. NCMBJ 2026; 16 (62) :1-22
URL: http://ncmbjpiau.ir/article-1-1806-en.html
URL: http://ncmbjpiau.ir/article-1-1806-en.html
Tissue Engineering and Regenerative Medicine Research Center, New Health Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
Abstract: (659 Views)
Extended Abstract
Background and Aim: Diabetes mellitus is a growing global health crisis, with a prevalence exceeding 537 million people in 2023 and projections of over 700 million by 2045, urgently demanding innovative therapeutic strategies. Current treatments, such as insulin therapy, oral hypoglycemic agents, and pancreas or islet transplantation, despite providing partial glycemic control, fail to restore the physiological function of pancreatic β-cells. However, these approaches are limited by high costs, lifelong dependency, immunosuppression-related complications, severe donor shortages, and inability to prevent progressive beta-cell destruction. In this context, cell therapy aimed at replacing damaged beta cells and restoring glucose-dependent insulin secretion represents a promising approach.
Materials and Methods: Among various cell sources, mesenchymal stem cells (MSCs) have attracted special attention due to their easy accessibility (from adipose tissue, bone marrow, and umbilical cord), high proliferation capacity, potent immunomodulatory properties (via inhibition of T lymphocytes and induction of the M2 macrophage phenotype), and multilineage differentiation potential. However, conventional chemical differentiation protocols relying on expensive and unstable growth factors (e.g., Activin A, FGF10, Retinoic Acid, Exendin‑4) often lead to heterogeneous cell populations with incomplete functional maturation and poor glucose responsiveness. In response to these challenges, novel approaches based on physical and mechanical signals have been developed recently. Results: Parameters such as substrate stiffness in the range of 1–5 kPa (similar to native pancreatic tissue), surface nanotopography, three‑dimensional culture in biocompatible hydrogels, and advanced cell imprinting technology can activate mechanosensing and mechanotransduction pathways. These stimuli, via integrins, focal adhesion kinase (FAK), RhoA/ROCK pathways, and nuclear translocation of YAP/TAZ transcription factors, dramatically increase the expression of key genes such as PDX1, NKX6.1, and MAFA, and improve glucose-stimulated insulin secretion (GSIS).
Conclusion: Studies have shown that physical differentiation produces more mature, stable, and functional β-like cells that closely resemble native β cells, compared to chemical methods. Accordingly, the synergistic combination of chemical and physical stimuli, together with smart biomaterials and microfluidic technologies, can provide an optimal, safe, and industrially scalable (under GMP conditions) strategy for generating functional beta cells. Such an approach would revolutionize the treatment of type 1 diabetes, bringing hope of a life free from insulin injections and chronic complications to millions of patients worldwide.
Background and Aim: Diabetes mellitus is a growing global health crisis, with a prevalence exceeding 537 million people in 2023 and projections of over 700 million by 2045, urgently demanding innovative therapeutic strategies. Current treatments, such as insulin therapy, oral hypoglycemic agents, and pancreas or islet transplantation, despite providing partial glycemic control, fail to restore the physiological function of pancreatic β-cells. However, these approaches are limited by high costs, lifelong dependency, immunosuppression-related complications, severe donor shortages, and inability to prevent progressive beta-cell destruction. In this context, cell therapy aimed at replacing damaged beta cells and restoring glucose-dependent insulin secretion represents a promising approach.
Materials and Methods: Among various cell sources, mesenchymal stem cells (MSCs) have attracted special attention due to their easy accessibility (from adipose tissue, bone marrow, and umbilical cord), high proliferation capacity, potent immunomodulatory properties (via inhibition of T lymphocytes and induction of the M2 macrophage phenotype), and multilineage differentiation potential. However, conventional chemical differentiation protocols relying on expensive and unstable growth factors (e.g., Activin A, FGF10, Retinoic Acid, Exendin‑4) often lead to heterogeneous cell populations with incomplete functional maturation and poor glucose responsiveness. In response to these challenges, novel approaches based on physical and mechanical signals have been developed recently. Results: Parameters such as substrate stiffness in the range of 1–5 kPa (similar to native pancreatic tissue), surface nanotopography, three‑dimensional culture in biocompatible hydrogels, and advanced cell imprinting technology can activate mechanosensing and mechanotransduction pathways. These stimuli, via integrins, focal adhesion kinase (FAK), RhoA/ROCK pathways, and nuclear translocation of YAP/TAZ transcription factors, dramatically increase the expression of key genes such as PDX1, NKX6.1, and MAFA, and improve glucose-stimulated insulin secretion (GSIS).
Conclusion: Studies have shown that physical differentiation produces more mature, stable, and functional β-like cells that closely resemble native β cells, compared to chemical methods. Accordingly, the synergistic combination of chemical and physical stimuli, together with smart biomaterials and microfluidic technologies, can provide an optimal, safe, and industrially scalable (under GMP conditions) strategy for generating functional beta cells. Such an approach would revolutionize the treatment of type 1 diabetes, bringing hope of a life free from insulin injections and chronic complications to millions of patients worldwide.
Keywords: Diabetes, Cell therapy, Mesenchymal stem cells, Chemical differentiation, Physical differentiation, Growth factors, Cell imprinting
Type of Study: Review Article |
Subject:
Cellular and molecular
Received: 2026/05/31 | Accepted: 2026/05/31 | Published: 2026/05/31
Received: 2026/05/31 | Accepted: 2026/05/31 | Published: 2026/05/31
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