Hematopoietic stem and progenitor cells derived platelet lysate promotes diabetic wound healing

BACKGROUND: Diabetic wounds represent an escalating clinical challenge driven by the rising global prevalence of diabetes and the lack of effective treatments. Platelets serve as natural reservoirs of diverse growth factors, holding considerable promise for promoting tissue regeneration and wound repair. However, current platelet-derived therapies are constrained by donor dependence, protocol variability, and inconsistent product quality. METHODS: This study established an efficient in vitro protocol for generating functional platelets from human hematopoietic stem and progenitor cells (HSPCs). These regenerative platelets were subsequently lysed to produce induced human platelet lysate (ihPL). The contents of key growth factors in ihPL and human peripheral blood platelet lysate (hPL) were compared by enzyme-linked immunosorbent assay (ELISA). We established diabetic mice wound model to evaluate the therapeutic efficacy of ihPL on wound healing. Furthermore, in vitro experiments assessed the effects of ihPL on dermal fibroblasts proliferation, migration, and collagen synthesis. Transcriptome sequencing and Western blot (WB) were employed to elucidate the underlying signaling pathways. RESULTS: HSPCs differentiation into megakaryocytes exceeded 80%, with a subsequent platelet production efficiency of 38.3% ± 5.35%. ELISA revealed that the concentrations of fibroblast growth factor (140.1 ± 0.986 vs. 1.0 ± 0.008) and vascular endothelial growth factor (12.74 ± 5.280 vs. 1.0 ± 0.276) were significantly elevated in ihPL compared with hPL. In diabetic mice, ihPL (89.44% ± 9.83%), hPL (73.60% ± 12.21%), and epidermal growth factor (EGF, 59.72% ± 12.87%) significantly accelerated wound closure compared with the vehicle control group (43.53% ± 16.09%) at day 14 (P < 0.05). Notably, ihPL demonstrated superior efficacy relative to both hPL and EGF (P < 0.05). Histological analysis and Optical coherence tomography angiography confirmed enhanced extracellular matrix deposition and angiogenesis with ihPL versus vehicle control. Furthermore, ihPL significantly promoted dermal fibroblasts proliferation, migration, and collagen synthesis in vitro. Transcriptome analyses indicated activation of multiple tissue regeneration-associated signaling pathways and WB further confirmed the upregulation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway representing a potential underlying mechanism. CONCLUSION: This study establishes a standardized, donor-independent, and immunologically safer cell-based therapeutic strategy for diabetic wound management, with considerable potential for clinical translation.