Mechanical Memory Impairs Adipose-Derived Stem Cell (ASC) Adipogenic Capacity After Long-Term In Vitro Expansion.

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)

Introduction Adipose derived stem cells (ASCs) hold great promise for clinical applications such as soft tissue regeneration and for in vitro tissue models and are notably easy to derive in large numbers. Specifically, ASCs provide an advantage for in vitro models of adipose tissue, where they can be employed as tissue specific cells and for patient specific models. However, ASC in vitro expansion may unintentionally reduce adipogenic capacity due to the stiffness of tissue culture plastic (TCPS). Methods Here, we expanded freshly isolated ASCs on soft and stiff substrates for 4 passages before adipogenic differentiation. At the last passage we swapped the substrate from stiff to soft, or soft to stiff to determine if short term exposure to a different substrate altered adipogenic capacity. Results Expansion on stiff substrates reduced adipogenic capacity by 50% which was not rescued by swapping to a soft substrate for the last passage. Stiff substrates had greater nuclear area and gene expression of nesprin-2, a protein that mediates the tension of the nuclear envelope by tethering it to the actin cytoskeleton. Upon swapping to a soft substrate, the nuclear area was reduced but nesprin-2 levels did not fully recover, which differentially regulated cell commitment transcriptional factors. Conclusion Therefore, in vitro expansion on stiff substrates must be carefully considered

Evidence level

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

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