Optimization of Non-Cross-Linked Hyaluronic Acid and Adipose-Derived Mesenchymal Stem Cells for Regenerative Applications: an in Vitro Study.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Hyaluronic acid (HA) and adipose-derived mesenchymal stem cells (AD-MSCs) are both promising agents for skin rejuvenation. Combining non-cross-linked HA with AD-MSCs may enhance regenerative outcomes; however, the optimal HA concentration and its compatibility with AD-MSCs remain unclear. This study evaluated AD-MSCs encapsulated in varying concentrations of non-cross-linked HA, including a Proage® HA formulation, to identify the most biocompatible scaffold for regenerative applications. AD-MSCs were isolated from human adipose tissue and characterized using flow cytometry and tri-lineage differentiation. Cells were encapsulated in HA matrices ranging from 2% to 10%, including a Proage® 2% HA formulation. Metabolic activity was assessed using the Alamar Blue assay on Days 1, 3, 5, and 7. Gene expression of COL1A1, COL3A1, LMNA, IL10, TIMP1, MMP1, CD49f, and CD146 was analyzed via qRT-PCR to evaluate extracellular matrix remodeling and inflammatory responses. AD-MSCs maintained high metabolic activity across HA concentrations, with 4% HA demonstrating the highest metabolic activity by Day 5, whereas higher concentrations (>5%) reduced activity. Gene expression analysis showed significant upregulation of COL1A1, COL3A1, LMNA, TIMP1, CD49f, and CD146 in 3D HA conditions compared with 2D culture. Specifically, 4% HA increased COL1A1, LMNA, CD146, and TIMP1 expression, while the Pro

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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