scholarly journals Evaluation of the effects of human dental pulp stem cells on the biological phenotype of hypertrophic keloid fibroblasts

Author(s):  
Ling-ling Fu ◽  
Ming Yan ◽  
Ola A. Nada ◽  
Li-ming Chen ◽  
Martin Gosau ◽  
...  

Abstract Background Despite numerous existing treatments for keloids, the responses in the clinic have been disappointing due to either low efficacy or side effects. Numerous studies dealing with preclinical and clinical trials have been published about effective therapies for fibrotic diseases using mesenchymal stem cells, However, no research has yet been reported to scientifically investigate the effect of HDPSCs on the treatment of keloids.The objective is to provide an experimental basis to provide a novel proposal for the application of stem cells in the treatment of keloids.Methods HNFs and HKFs were cultured alone and in combination with DPSCs using a trans-well cell-contact-independent cell culture system. The effects of DPSCs on HKFs were tested using CCK-8 assay, Live/dead staining assay, quantitative polymerase chain reaction, Western blot.Result DPSCs don’t inhibited HKFs and HNFs proliferation and induce apoptosis, but inhibited migration. Furthermore, DPSCs significantly decreased expression of profibrotic genes, transforming growth factor-β 1,and transforming growth factor-β 2. DPSCs suppressed the ECM synthesis in HKFs, as indicated by decreased expression of collagen I and fibronectin and low levels of hydroxyproline in cell culture supernatant. Conclusions 1) Co-culture of DPSCs inhibits the migration of HKFs but does not affect the proliferation and apoptosis of HKFs.2) DPSCs co-culture inhibits the expression of pro-fibrotic genes and promotes the expression of anti-fibrotic genes in HKFs.3) DPSCs co-culture inhibits the synthesis of extracellular matrix by HKFs.

2021 ◽  
Author(s):  
Ling-ling Fu ◽  
Ming Yan ◽  
Ola A. Nada ◽  
Li-ming Chen ◽  
Martin Gosau ◽  
...  

Abstract Background Despite numerous existing treatments for keloids, the responses in the clinic have been disappointing due to either low efficacy or side effects. Numerous studies dealing with preclinical and clinical trials have been published about effective therapies for fibrotic diseases using mesenchymal stem cells, However, no research has yet been reported to scientifically investigate the effect of HDPSCs on the treatment of keloids.The objective is to provide an experimental basis to provide a novel proposal for the application of stem cells in the treatment of keloids.Methods HNFs and HKFs were cultured alone and in combination with DPSCs using a trans-well cell-contact-independent cell culture system. The effects of DPSCs on HKFs were tested using CCK-8 assay, Live/dead staining assay, quantitative polymerase chain reaction, Western blot.Results DPSCs don’t inhibited HKFs and HNFs proliferation and induce apoptosis, but inhibited migration. Furthermore, DPSCs significantly decreased expression of profibrotic genes, transforming growth factor-β 1,and transforming growth factor-β 2. DPSCs suppressed the ECM synthesis in HKFs, as indicated by decreased expression of collagen I and fibronectin and low levels of hydroxyproline in cell culture supernatant. Conclusions 1) Co-culture of DPSCs inhibits the migration of HKFs but does not affect the proliferation and apoptosis of HKFs.2) DPSCs co-culture inhibits the expression of pro-fibrotic genes and promotes the expression of anti-fibrotic genes in HKFs.3) DPSCs co-culture inhibits the synthesis of extracellular matrix by HKFs.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1803
Author(s):  
Ming Yan ◽  
Ling-Ling Fu ◽  
Ola A. Nada ◽  
Li-Ming Chen ◽  
Martin Gosau ◽  
...  

Objective: Despite numerous existing treatments for keloids, the responses in the clinic have been disappointing, due to either low efficacy or side effects. Numerous studies dealing with preclinical and clinical trials have been published about effective therapies for fibrotic diseases using mesenchymal stem cells; however, no research has yet been reported to scientifically investigate the effect of human dental pulp stem cells (HDPSCs) on the treatment of keloids. The objective is to provide an experimental basis for the application of stem cells in the treatment of keloids. Methods: Human normal fibroblasts (HNFs) and human keloid fibroblasts (HKFs) were cultured alone and in combination with HDPSCs using a transwell cell-contact-independent cell culture system. The effects of HDPSCs on HKFs were tested using a CCK-8 assay, live/dead staining assay, quantitative polymerase chain reaction, Western blot and immunofluorescence microscopy. Results: HDPSCs did not inhibit the proliferation nor the apoptosis of HKFs and HNFs. HDPSCs did, however, inhibit their migration. Furthermore, HDPSCs significantly decreased the expression of profibrotic genes (CTGF, TGF-β1 and TGF-β2) in HKFs and KNFs (p < 0.05), except for CTGF in HNFs. Moreover, HDPSCs suppressed the extracellular matrix (ECM) synthesis in HKFs, as indicated by the decreased expression of collagen I as well as the low levels of hydroxyproline in the cell culture supernatant (p < 0.05). Conclusions: The co-culture of HDPSCs inhibits the migration of HKFs and the expression of pro-fibrotic genes, while promoting the expression of anti-fibrotic genes. HDPSCs’ co-culture also inhibits the synthesis of the extracellular matrix by HKFs, whereas it does not affect the proliferation and apoptosis of HKFs. Therefore, it can be concluded that HDPSCs can themselves be used as a tool for restraining/hindering the initiation or progression of fibrotic tissue.


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