Engineering a synthetic niche for hADSC preconditioning with PRP, Lp-SN, and resveratrol nanoparticles

Ex vivo expansion of human adipose-derived stem cells (hADSCs) remains challenging because reduced-serum culture conditions can compromise short-term cell function. Here, we evaluated a microenvironment-inspired tri-component preconditioning regimen composed of platelet-rich plasma (PRP), Lactobacillus plantarum cell-free supernatant (Lp-SN), and resveratrol-loaded PLGA nanoparticles (RSV-PLGA-NPs) as a reduced-serum culture support strategy. Using a Box-Behnken design, we identified a formulation space in which PRP, Lp-SN, and RSV-PLGA-NPs were associated with improved hADSC viability and increased expression of selected stemness-associated genes in vitro. Omission-control experiments comparing the full formulation with partial combinations and blank PLGA NPs showed attenuated responses when individual components were removed, whereas the NP carrier alone had no significant effect. These findings support the utility of this tri-component system as a preliminary ex vivo preconditioning approach for short-term hADSC culture support. However, the results should be interpreted within the limits of the present in vitro study, as long-term expansion, post-treatment differentiation capacity, and in vivo performance were not evaluated.