Optimized Metabolic Conditions Reveal the Adipogenic Competence of Wharton’s Jelly MSCs: Insight from Literature Review and Experimental Validation

Mesenchymal stromal/stem cells (MSCs) derived from distinct tissue niches exhibit marked functional heterogeneity, yet the determinants governing their adipogenic competence remain incompletely understood. Wharton's jelly MSCs (WJ-MSCs) are frequently considered poorly adipogenic compared with bone marrow MSCs (BM-MSCs), although the contribution of culture conditions to this phenotype has not been systematically investigated. Here, integrating a structured review of 41 studies with experimental modeling, we demonstrate that adipogenic commitment of WJ-MSCs is highly dependent on metabolic induction conditions and exposure duration. Structured literature review revealed substantial heterogeneity in adipogenic protocols across the literature, with no consensus framework for WJ-MSCs differentiation. Guided by these observations, we compared four adipogenic conditions differing in glucose availability and insulin supplementation and quantified differentiation using machine learning-assisted lipid imaging. Whereas BM-MSCs readily underwent adipogenesis under conventional induction conditions, WJ-MSCs displayed delayed and limited differentiation. However, prolonged induction combined with enhanced metabolic support revealed a delayed but significant adipogenic responsiveness for WJ-MSCs. High glucose and insulin synergistically promoted lipid accumulation in both MSCs sources, with the strongest effects observed under combined conditions. These findings identify metabolic context as a critical regulator of MSCs lineage plasticity and establish a standardized framework for evaluating adipogenic differentiation across tissue-derived MSCs populations.