Carboxymethylcellulose Activates Dermal Cells and Adipose-Derived Stem Cells Through Wnt/β-catenin Pathway

Author(s): Dongyi Peng, Amanda B. Reed-Maldonado, Lia Banie, Guifang Wang, Guiting Lin and Tom F. Lue

Background: Carboxymethylcellulose (CMC) is an inexpensive biomaterial that has been used for wound dressings and as an excipient for drug therapy. CMC in combination with adipose-derived stem cells has been reported to enhance tissue healing. The mechanisms underlying this effect are poorly understood.

Objective: To investigate the effects of CMC and BloodSTOP iX (BSiX) on porcine dermal cells (PDCs) and porcine adipose-derived stem cells (PADSCs) to define the mechanisms of CMC in activating PDCs and PADSCs. Methods: A young pig was used to isolate PDCs and PADSCs. PDCs were treated with different concentrations of CMC, BloodSTOP (BS), and BSiX. Expression of phosphorylated histone 3 (H3P) and cell proliferation were then assessed. To explore the mechanisms of CMC in activating PDCs and PADSCs, the cells were treated with different concentrations of CMC (0,10,100,1000μg/ml), and Western blot was used to measure the proteins of the Wnt/β-catenin pathway.

Results: CMC and BSiX had significant effects in promoting PDC cell growth, while the effect of BS was minor. Both CMC and BSiX promoted PDCs mitosis in vitro; BSiX at a concentration of 100μg/ml had the best effect. Both CMC and BSiX promoted PDC proliferation in a dose-dependent manner, but the effect from BSiX was much greater than that of CMC. CMC activated AMPK in both PDCs and PADSCs. AMPK by crosstalking with Wnt/β-catenin, activated AMPK promotes the expression of its downstream genes, such as H3P and Cyclin D1.

Conclusion: We successfully isolated and cultured PDCs and PADSCs. We found that both CMC and BSiX promoted PDC mitosis and proliferation in a dose-dependent manner. In both PDC and PADSC, CMC activated Wnt/β-catenin signaling pathway through AMPK. This could be the underlying mechanism by which CMC activates stem cells and dermal cells to promote wound