Mechanisms and Drug-Augmenting Strategies of Mesenchymal Stem Cells for Preserving β-Cell in Type 2 Diabetes

Area of Science:

• Endocrinology
• Stem Cell Biology
• Immunology

Background:

• Type 2 diabetes (T2D) is characterized by progressive pancreatic beta-cell dysfunction.
• Preserving beta-cell function is a key therapeutic target for managing T2D.
• Mesenchymal stem cells (MSCs) show significant potential in protecting beta-cells.

Purpose of the Study:

• To systematically review the mechanisms by which MSCs protect pancreatic beta-cell function in T2D.
• To explore pharmacological strategies for enhancing MSC efficacy in T2D treatment.
• To propose future research directions for MSC-based T2D therapies.

Main Methods:

• Systematic literature review of MSC mechanisms in T2D.
• Integration of eight core protective mechanisms of MSCs.
• Analysis of pharmacological interventions and future research avenues.

Main Results:

• MSCs protect beta-cells through eight integrated mechanisms: immune modulation, anti-inflammation, antioxidant effects, enhanced autophagy, ER stress alleviation, mitochondrial protection, regeneration, and ferroptosis inhibition.
• MSC effects operate across three functional levels: injury elimination, homeostasis maintenance, and cell fate intervention.
• Pharmacological agents and natural products can enhance MSC efficacy, but clinical translation faces barriers.

Conclusions:

• MSCs provide a multi-layered, networked intervention system for preserving beta-cell function in T2D.
• Optimizing MSC sources and engineering MSC-derived exosomes are crucial future research directions.
• This review offers a theoretical basis for developing novel MSC-based T2D therapies.