Hypoxia-induced HIF-1α accumulation promotes superior tenogenic differentiation potential of human adipose-derived mesenchymal stromal cells.

Early human evidence such as case series or small samples is exploring possible benefits.

• 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)

Tendon injuries remains a challenge to treat owing to its poor intrinsic reparative ability. It is hypothesised that hypoxic conditioning of mesenchymal stem cells (MSC) through the activation of hypoxia-inducible factor-1 alpha (HIF-1α), may enhance tendon repair process by promoting cellular proliferation and tenogenic differentiation. To demonstrate this, a study using roxadustat, a specific hypoxia mimetic mediator and HIF-1α inducer was conducted on adipose-derived mesenchymal stromal cells (AD-MSCs). Cellular morphology, proliferation rates, tenogenic protein and gene expression levels in untreated AD-MSCs (Group 1), roxadustat pre-conditioned AD-MSCs (Group 2), AD-MSCs subjected to CAY10585 (Group 3), roxadustat pre-conditioned AD-MSCs with CAY10585 (Group 4) and untreated primary tenocytes (Group 5) were evaluated. MSCs pre-conditioned with 12.5µM roxadustat for 24 hours showed the highest expression of HIF-1α without affecting the proliferation rates of AD-MSCs. However, significant reduction of HIF-1α levels was observed when the cells were treated with 3.5µM CAY10585. Roxadustat significantly up-regulated collagen I and III expressions by 6.6 and 6.3-fold respectively. HIF-1α promoted Scleraxis , Tenascin-C and Collagen III expressions, resulting in an increase of 6, 7, and 3 folds respectively. Conversely, using CAY10585 reduced these expressions to 3, 2 and 1 folds

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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