Adipose‑derived mesenchymal stem cells inhibit cell proliferation and migration and suppress extracellular matrix synthesis in hypertrophic‑scar and keloid fibroblasts

Keloid is a type of unusually raised scar. Botulinum toxin A (BTX-A) has a great application potential in keloids treatment. Here, we investigated the functional role of BTX-A in keloids. We separated keloid tissues and normal skin tissues from keloid patients and found that the expression of myofibroblast markers, α-SMA, Collagen I, and Collagen III was increased in the keloid tissues as compared with normal skin tissues. Keloid fibroblasts derived from keloid tissues were treated with TGF-β1 to induce the differentiation of fibroblasts into myofibroblasts. The keloid myofibroblasts displayed a significant up-regulation of α-SMA. BTX-A enhanced the expression of adipocyte markers, PPARγ and C/EBPα, and increased the accumulation of lipid droplets, and reduced the expression of α-SMA, Collagen I, and Collagen III in the keloid myofibroblasts. Moreover, BTX-A enhanced the expression of BMP4 and p-smad1/5/8. Noggin (BMP4 antagonist) treatment reversed BTX-A-mediated increase of PPARγ and C/EBPα expression and lipid droplets, and down-regulation of α-SMA, Collagen I, and Collagen III in primary keloid myofibroblasts. In conclusion, BTX-A promoted the transdifferentiation of primary keloid myofibroblasts into adipocyte-like cells, which may attribute to activate BMP4/Smad signalling pathway. Thus, this study provides new insights into the mechanism of BTX-A in keloid.

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“…α-SMA, Collagen I, and Collagen III are ECM-related proteins. 20 Thus, ECM deposition was increased in keloid tissues.…”

Section: Discussionmentioning

confidence: 98%

Botulinum toxin A promotes the transdifferentiation of primary keloid myofibroblasts into adipocyte‐like cells

Dai

Lei

2021

Basic Clin Pharma Tox

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“…Numerous studies dealing with preclinical and clinical trials have been published about effective therapies for fibrotic diseases using mesenchymal stem cells, including the following: bone-marrow-derived mesenchymal stem cells (BMSCs) [ 8 , 9 , 10 ] and adipose derived mesenchymal stem cells (ADSCs) [ 11 ]. Human dental pulp stem cells (HDPSCs) are a type of adult stem cell that possess self-renewal, self-replication and multi-differentiation properties, where they can differentiate into a variety of mesodermal tissue cells, such as chondrocytes, osteoblasts, cardiomyocytes as well as adipocytes [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Effects of Human Dental Pulp Stem Cells on the Biological Phenotype of Hypertrophic Keloid Fibroblasts

Yan

Nada

et al. 2021

Cells

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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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“…Numerous studies dealing with preclinical and clinical trials have been published about effective therapies for brotic diseases using mesenchymal stem cells, including the following: bone marrow derived mesenchymal stem cells (BMSCs) [8], adipose derived mesenchymal stem cells (ADSCs) [9].…”

Section: Introductionmentioning

confidence: 99%

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

Yan

Nada

et al. 2021

Preprint

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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.

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Adipose‑derived mesenchymal stem cells inhibit cell proliferation and migration and suppress extracellular matrix synthesis in hypertrophic‑scar and keloid fibroblasts

Cited by 18 publications

References 45 publications

Botulinum toxin A promotes the transdifferentiation of primary keloid myofibroblasts into adipocyte‐like cells

Botulinum toxin A promotes the transdifferentiation of primary keloid myofibroblasts into adipocyte‐like cells

Evaluation of the Effects of Human Dental Pulp Stem Cells on the Biological Phenotype of Hypertrophic Keloid Fibroblasts

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

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