Preconditioning strategies for stem cells and exosomes: Transformative potential in diabetic wound treatment: A...

Diabetic wounds pose a significant clinical challenge due to impaired healing processes driven by poor circulation, neuropathy, and immune dysfunction. Adipose-derived stem cells (ADSCs) and mesenchymal stem cells (MSCs) offer promising therapeutic potential due to their multilineage differentiation and paracrine effects that promote tissue regeneration. However, the harsh wound environment necessitates innovative strategies to enhance their therapeutic efficacy. This review explores various preconditioning strategies, including hypoxic, pharmacological, cytokine, and carrier systems, that enhance the survival, proliferation, and function of ADSCs and MSCs. The integration of advanced biomaterials such as hydrogels and scaffolds further supports cell viability and function, offering potential solutions for improved diabetic wound healing. Recent advances and future directions in the optimization of these strategies are discussed, emphasizing their potential to transform stem cell therapies for diabetic wounds. We highlight that specific preconditioning methods-such as hypoxia and pharmacological agents like metformin or empagliflozin-can selectively enhance exosomal miRNA cargo (e.g., miR-126, miR-139-3p) and downstream angiogenic signaling.Our synthesis underscores the superior translational potential of ADSC-derived exosomes over cell therapies, especially when optimized via preconditioning tailored to the diabetic microenvironment.