scholarly journals Substances Secreted by Starved Human Dermal Fibroblasts Enhancing the Wound Healing Process in Rat without Scar: A Potential Acellular System for Wound Healing

Author(s):  
Pejman Hanifi-Moghaddam ◽  
Amrollah Mostafazadeh
1999 ◽  
Vol 69 (2) ◽  
pp. 113-119 ◽  
Author(s):  
Weimann ◽  
Hermann

The effect of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts from three different donors was investigated. The migration of cells into a wounded area was dose-dependently stimulated by Ca D-pantothenate. The number of cells that migrated across the edge of the wound increased from 32 ± 7 cells/ mm without Ca D-pantothenate to 76 ± 2 cells/ mm with 100 mg/ml Ca D-pantothenate. Moreover, the mean migration distance per cell increased from 0.23 ± 0.05 mm to 0.33 ± 0.02 mm. The mean migration speed was calculated to be 10.5 mm/hour without and 15 mm/hour with Ca D-pantothenate. Cell proliferation was also dose-dependently stimulated. The final cell densities were 1.2 to 1.6-fold higher in cultures containing 100 mg/ml Ca D-pantothenate. The protein synthesis was modulated, since two unidentified proteins were more strongly expressed in pantothenate supplemented cultures. In conclusion, Ca D-pantothenate accelerates the wound healing process by increasing the number of migrating cells, their distance and hence their speed. In addition, cell division is increased and the protein synthesis changed. These results suggest that higher quantities of pantothenate are locally required to enhance wound healing.


2021 ◽  
Vol 14 (4) ◽  
pp. 301
Author(s):  
Yayoi Kawano ◽  
Viorica Patrulea ◽  
Emmanuelle Sublet ◽  
Gerrit Borchard ◽  
Takuya Iyoda ◽  
...  

Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.


2019 ◽  
Vol 2019 ◽  
pp. 1-20 ◽  
Author(s):  
Sarah D’Alessandro ◽  
Andrea Magnavacca ◽  
Federica Perego ◽  
Marco Fumagalli ◽  
Enrico Sangiovanni ◽  
...  

Wound healing is a complex process regulated by multiple signals and consisting of several phases known as haemostasis, inflammation, proliferation, and remodelling. Keratinocytes, endothelial cells, macrophages, and fibroblasts are the major cell populations involved in wound healing process. Hypoxia plays a critical role in this process since cells sense and respond to hypoxic conditions by changing gene expression. This study assessed the in vitro expression of 77 genes involved in angiogenesis, metabolism, cell growth, proliferation and apoptosis in human keratinocytes (HaCaT), microvascular endothelial cells (HMEC-1), differentiated macrophages (THP-1), and dermal fibroblasts (HDF). Results indicated that the gene expression profiles induced by hypoxia were cell-type specific. In HMEC-1 and differentiated THP-1, most of the genes modulated by hypoxia encode proteins involved in angiogenesis or belonging to cytokines and growth factors. In HaCaT and HDF, hypoxia mainly affected the expression of genes encoding proteins involved in cell metabolism. This work can help to enlarge the current knowledge about the mechanisms through which a hypoxic environment influences wound healing processes at the molecular level.


2020 ◽  
pp. 153537022097426
Author(s):  
Yeon S Kim ◽  
Hye-Young Lee ◽  
Jeon Y Jang ◽  
Hye R Lee ◽  
Yoo S Shin ◽  
...  

Intractable wound healing is the habitual problem of diabetes mellitus. High blood glucose limits wound healing by interrupting inflammatory responses and inhibiting neoangiogenesis. Oxidative stress is commonly thought to be a major pathogenic cause of diabetic complications. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one, EDV) is a free radical scavenger which suppress oxidative stress. This study investigates whether EDV can reduce oxidative stress in wound healing HaCaT/human dermal fibroblasts cells (HDFs) in vitro and in vivo animal model. Cell viability and wound healing assays, FACS flow cytometry, and Hoechst 33342 staining were performed to confirm apoptosis and cytotoxicity in H2O2 and EDV-treated HaCaT and HDFs. A streptozotocin-induced hyperglycemic animal model was made in adult C57BL6 mice. Full-thickness skin flap was made on dorsomedial back and re-sutured to evaluate the wound healing process. EDV was delivered slowly in the skin flap with degradable fibrin glue. The flap was monitored and analyzed on postoperative days 1, 3, and 5. CD31/DAPI staining was done to detect newly formed blood vessels. The expression levels of NF-κB, bcl-2, NOX3, and STAT3 proteins in C57BL6 mouse tissues were also examined. The wound healing process in hyper- and normoglycemic mice showed a difference in protein expression, especially in oxidative stress management and angiogenesis. Exogenous H2O2 reduced cell viability in a proportion to the concentration via apoptosis. EDV protected HaCaT cells and HDFs from H2O2 induced reactive oxygen species cell damage and apoptosis. In the mouse model, EDV with fibrin resulted in less necrotic areas and increased angiogenesis on postoperative day 5, compared to sham-treated mice. Our results indicate that EDV could protect H2O2-induced cellular injury via inhibiting early apoptosis and inflammation and also increasing angiogenesis. EDV might be valuable in the treatment of diabetic wounds that oxidative stress has been implicated.


2021 ◽  
Vol 22 (11) ◽  
pp. 5571
Author(s):  
Jaeyoon Kim ◽  
Jae Young Shin ◽  
Yun-Ho Choi ◽  
So Young Lee ◽  
Mu Hyun Jin ◽  
...  

Adenosine is a cellular metabolite with diverse derivatives that possesses a wide range of physiological roles. We investigated the molecular mechanisms of adenosine and cordycepin for their promoting effects in wound-healing process. The mitochondrial energy metabolism and cell proliferation markers, cAMP responsive element binding protein 1 (CREB1) and Ki67, were enhanced by adenosine and cordycepin in cultured dermal fibroblasts. Adenosine and cordycepin stimulated adenosine receptor signaling via elevated cAMP. The phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3 beta (Gsk3b) and Wnt target genes such as bone morphogenetic protein (BMP) 2/4 and lymphoid enhancer binding factor (Lef) 1 were activated. The enhanced gene expression by adenosine and cordycepin was abrogated by adenosine A2A and A2B receptor inhibitors, ZM241385 and PSH603, and protein kinase A (PKA) inhibitor H89, indicating the involvement of adenosine receptor A2A, A2B and PKA. As a result of Wnt/β-catenin pathway activation, the secretion of growth factors such as insulin-like growth factor (IGF)-1 and transforming growth factor beta (TGFβ) 3 was increased, previously reported to facilitate the wound healing process. In addition, in vitro fibroblast migration was also increased, demonstrating their possible roles in facilitating the wound healing process. In conclusion, our data strongly demonstrate that adenosine and cordycepin stimulate the Wnt/β-catenin signaling through the activation of adenosine receptor, possibly promoting the tissue remodeling process and suggest their therapeutic potential for treating skin wounds.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Jiajia Zhao ◽  
Li Hu ◽  
Jiarong Liu ◽  
Niya Gong ◽  
Lili Chen

Although adipose stem cell-conditioned medium (ASC-CM) has demonstrated the effect of promoting the cutaneous wound healing, the mechanism for this response on the effector cells (e.g., dermal fibroblasts) during the process remains to be determined. In this study, we aim to investigate the types and contents of cytokines in ASC-CM and the effects of some kinds of common cytokines in ASC-CM, such as EGF, PDGF-AA, VEGF, and bFGF, on dermal fibroblasts proliferation and migration in wound healing process. Results showed that these four cytokines had high concentrations in ASC-CM. The migration of skin fibroblasts could be significantly stimulated by VEGF, bFGF, and PDGF-AA, and the proliferation could be significantly stimulated by bFGF and EGF in ASC-CM. Additionally, ASC-CM had more obvious promoting effect on fibroblasts proliferation and migration than single cytokine. These observations suggested that ASC-CM played an important role in the cutaneous injury partly by the synergistic actions of several cytokines in promoting dermal fibroblasts proliferation and migration, and ASC-CM was more adaptive than each single cytokine to be applied in promoting the wound healing.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Peng Liu ◽  
Yi Zhu ◽  
Qin Li ◽  
Biao Cheng

A diabetic nonhealing wound causes heavy economic burden and compromised quality of life in patients. The human dermal fibroblast (HDF), which is an important kind of effector cell in the wound healing process, represents different biological behaviors in the normal and diabetic skins. Given this, we attempt to explore functional changes in diabetic skin-derived HDFs and try to find out the “hub” genes that modulate diabetic HDFs and may be the potential therapeutic targets of diabetic wound healing. We searched the GEO database for related miRNA (GSE68185, GSE84971) and mRNA (GSE49566, GSE78891) profiles. After eliminating batch effects and identifying differentially expressed genes (DEGs), we applied enrichment analyses and found that 3 miRNAs and 30 mRNAs were differentially expressed in diabetic HDFs. Enrichment analyses showed that these genes are closely related to wound healing, for example, extracellular matrix (ECM) organization, angiogenesis, cell proliferation, and migration. Subsequently, we constructed the gene correlation network of DEGs to identify hub genes by merging the protein-protein interaction network, weighted gene coexpression network, and predicted miRNA-mRNA regulatory network. Based on the gene correlation network, we identified the top 3 hub genes: miR-181a-5p, POSTN, and CDH11. Among these, POSTN is a predicted target of miR-181a-5p and is supposed to work together with CDH11 as a functional group. Finally, we verified the expression pattern of the hub genes by in vitro quantification experiments in glucose-cultured HDFs. Our study suggested that miR-181a-5p possibly plays a key role in modulation of HDF behaviors during the diabetic state. However, the effects and mechanisms of miR-181a-5p in high glucose-cultured HDFs remain to be explored in the future.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Da Yong Shin ◽  
Ji-Ung Park ◽  
Min-Ha Choi ◽  
Sukwha Kim ◽  
Hyoun-Ee Kim ◽  
...  

Abstract Patients with diabetes experience delayed wound healing because of the uncontrolled glucose level in their bloodstream, which leads to impaired function of white blood cells, poor circulation, decreased production and repair of new blood vessels. Treatment using polydeoxyribonucleotide (PDRN), which is a DNA extracted from the sperm cells of salmon, has been introduced to accelerate the healing process of diabetic wounds. To accelerate the wound-healing process, sustained delivery of PDRN is critical. In this study, taking advantage of the non-invasive gelation property of alginate, PDRN was loaded inside the hydrogel (Alg-PDRN). The release behavior of PDRN was altered by controlling the crosslinking density of the Alg hydrogel. The amount of PDRN was the greatest inside the hydrogel with the highest crosslinking density because of the decreased diffusion. However, there was an optimal degree of crosslinking for the effective release of PDRN. In vitro studies using human dermal fibroblasts and diabetes mellitus fibroblasts and an in ovo chorioallantoic membrane assay confirmed that the Alg-PDRN hydrogel effectively induced cell proliferation and expression of angiogenic growth factors and promoted new blood vessel formation. Its effectiveness for accelerated diabetic wound healing was also confirmed in an in-vivo animal experiment using a diabetic mouse model.


2019 ◽  
Vol 2 (1) ◽  
pp. 14-17
Author(s):  
Nurul Aini Siagian ◽  
Syafira Nusaibah ◽  
Andayani Boang Manalu

Early mobilization includes factors that can affect the process of wound healing after surgery. Immediate mobilization in stages is very useful for the process of healing wounds and preventing infection and venous thrombosis. The purpose of this study was to determine whether there is a relationship between early mobilization and the process of healing wound post operative sectio caesarea at Sinar Husni General Hospital Medan Helvetia. The research design used was analytic survey with cross sectional approach. The sample in this study used the Consecutive Sampling method of data collection using a checklist sheet conducted on a sample of 19 respondents. The results of the study in this study are the majority of respondents who did early mobilization and who experienced rapid wound healing process as many as 4 people (21%) while the minority of respondents who did early mobilization and who experienced slow wound healing process were 1 person (5.3%). The majority of respondents who did not mobilize early and who experienced a slow wound healing process were 11 people (57.9%) and a minority who did not mobilize early and who experienced rapid healing as many as 4 people (21.1%). Statistical test results obtained p value = 0.046 <0.005. The conclusions of the results of this study indicate there is a relationship between early mobilization and the process of healing post operative sectio of caesarea. Suggestions The results of this study can be applied as a reference to improve nursing care services, especially in providing counseling and assistance to patients.


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