Effects of adipose-derived mesenchymal stem cell conditioned medium on human tenocytes exposed to high glucose

Introduction: Diabetic tendinopathy is a common invalidating and challenging disease that may be treated using stem cells. However, the effects of adipose-derived mesenchymal stem cell conditioned medium (ASC-CM) in diabetic tendinopathy have never been explored.Objectives: The present study evaluated the effects of ASC-CM on morphology, cell viability, structure, and scratch wound closure of human tenocytes (HTNC) exposed to high glucose (HG).Design: Experimental study.Methods: HTNC were exposed to HG (25 mM) for 7, 14 and 21 days with or without ASC-CM for the last 24 h. CM was collected from 4 x 10(5) ASCs, centrifuged for 10 min at 200 g and sterilized with 0.22 mu m syringe filter.Results: At 7 days, HG-HTNC had decreased cell viability [72 +/- 2%, p < 0.01 versus normal glucose (NG)] compared to NG-HTNC (90 +/- 5%). A further decrement was detected after 14 and 21 days (60 +/- 4% and 60 +/- 5%, both, p < 0.01 versus NG and p < 0.01 versus HG7). While NG-HTNC evidenced a normal fibroblast cell-like elongated morphology, HG-HTNC showed increased cell roundness. In contrast, HG-HTNC exposed to ASC-CM showed a significant increase in cell viability, an improved cell morphology and higher scratch wound closure at all HG time points. Moreover, the exposure to ASC-CM significantly increased thrombospondin 1 and transforming growth factor beta 1 (TGF-beta 1) content in HG-HTNC. The TGF-beta 1 elevation was paralleled by higher Collagen I and Vascular Endothelial Growth Factor in HG-HTNC.Conclusion: ASC-CM may restore the natural morphology, cell viability and structure of HTNC, promoting their scratch wound closure through TGF-beta 1 increase.