scholarly journals Dephosphorylation of Caveolin-1 Controls C-X-C Motif Chemokine Ligand 10 Secretion in Mesenchymal Stem Cells to Regulate the Process of Wound Healing

Author(s):  
Panpan Wang ◽  
Yingji Zhao ◽  
Juan Wang ◽  
Zhiying Wu ◽  
Bingdong Sui ◽  
...  

Mesenchymal stem cells (MSCs) secrete cytokines in a paracrine or autocrine manner to regulate immune response and tissue regeneration. Our previous research revealed that MSCs use the complex of Fas/Fas-associated phosphatase-1 (Fap-1)/caveolin-1 (Cav-1) mediated exocytotic process to regulate cytokine and small extracellular vesicles (EVs) secretion, which contributes to accelerated wound healing. However, the detailed underlying mechanism of cytokine secretion controlled by Cav-1 remains to be explored. We show that Gingiva-derived MSCs (GMSCs) could secrete more C-X-C motif chemokine ligand 10 (CXCL10) but showed lower phospho-Cav-1 (p-Cav-1) expression than skin-derived MSCs (SMSCs). Moreover, dephosphorylation of Cav-1 by a Src kinase inhibitor PP2 significantly enhances CXCL10 secretion, while activating phosphorylation of Cav-1 by H2O2 restraints CXCL10 secretion in GMSCs. We also found that Fas and Fap-1 contribute to the dephosphorylation of Cav-1 to elevate CXCL10 secretion. Tumor necrosis factor-α serves as an activator to up-regulate Fas, Fap-1, and down-regulate p-Cav-1 expression to promote CXCL10 release. Furthermore, local applying p-Cav-1 inhibitor PP2 could accelerate wound healing, reduce the expression of α-smooth muscle actin and increase cleaved-caspase 3 expression. These results indicated that dephosphorylation of Cav-1 could inhibit fibrosis during wound healing. The present study establishes a previously unknown role of p-Cav-1 in controlling cytokine release of MSC and may present a potential therapeutic approach for promoting scarless wound healing.

2018 ◽  
Vol 10 (432) ◽  
pp. eaai8524 ◽  
Author(s):  
Xiaoxing Kou ◽  
Xingtian Xu ◽  
Chider Chen ◽  
Maria Laura Sanmillan ◽  
Tao Cai ◽  
...  

Author(s):  
Hadi Sunarto ◽  
Setyo Trisnadi ◽  
Agung Putra ◽  
Nur Anna Chalimah Sa'dyah ◽  
Arya Tjipta ◽  
...  

Full-thickness wound are areas damage of skin associated with loss of epidermis and dermis. The wound healing mechanism consists proliferation, migration and remodeling. Hypoxic conditional medium of mesenchymal stem cells (HMSCs-CM) contains lots of soluble molecules, such as protein growth factor and cytokine anti-inflammation. The soluble molecule of HMSCs-CM plays a critical role in wound healing by upregulation of VEGF and collagen synthesis. The objective of this study was to evaluate the effect of HMSCs-CM on VEGF and collagen concentrations in rats with incised wounds. The methods of this study were an experimental animal study with post-test only control group design was performed involving 24 Wistar rats. The rats were randomized into four groups consisting of sham, control and two treatment groups (gel of HMSCs-CM at doses of 200 μL and 400 μL). The VEGF levels and collagen density were analyses using ELISA assay and Masson-trichome specific staining, respectively. One-way ANOVA and Post Hoc LSD were used to analyses the data. The results of this study showed that a VEGF levels was significant increased on day 6 with doses-dependent manner. Interestingly, the VEGF levels gradual decrease on day 9. In addition, the decreased of VEGF levels on day 9 in this study in line with our findings in which we found there was a trend in the decreased of collagen density, it indicated the completion of remodeling phase and there has been an acceleration in wound healing. This study demonstrated that HMSCs-CM were able to regulate VEGF levels and collagen synthesis in accelerate wound healing. The role of HMSCs-CM stimulate cutaneous wound healing should be clarified further.Keywords: hypoxic conditional medium of mesenchymal stem cells (HMSCs-CM), vascular endothelial growth factor, collagen synthesis, paracrine factors


2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
M. Isakson ◽  
C. de Blacam ◽  
D. Whelan ◽  
A. McArdle ◽  
A. J. P. Clover

Human skin is a remarkable organ that sustains insult and injury throughout life. The ability of skin to expeditiously repair wounds is paramount to survival. With an aging global population, coupled with a rise in the prevalence of conditions such as diabetes, chronic wounds represent a significant biomedical burden. Mesenchymal stem cells (MSC), a progenitor cell population of the mesoderm lineage, have been shown to be significant mediators in inflammatory environments. Preclinical studies of MSC in various animal wound healing models point towards a putative therapy. This review examines the body of evidence suggesting that MSC accelerate wound healing in both clinical and preclinical studies and also the possible mechanisms controlling its efficacy. The delivery of a cellular therapy to the masses presents many challenges from a safety, ethical, and regulatory point of view. Some of the issues surrounding the introduction of MSC as a medicinal product are also delineated in this review.


Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 878
Author(s):  
Frederick Robert Carrick ◽  
Luis Sebastian Alexis Valerio ◽  
Maxine N. Gonzalez-Vega ◽  
David Engel ◽  
Kiminobu Sugaya

Introduction: Wounds are associated with ranges of simple to complex disruption or damage to anatomical structure and function. They are also associated with enormous economic and social costs, increasing yearly, resulting in a severe impact on the wellbeing of individuals and society. Technology that might accelerate wound healing is associated with many benefits to injured people. Methods: BALBc mice underwent symmetrical excisional wounds through the panniculus carnosus. They were divided into a treatment group placed on an autonomous ceramic far-field infrared blanket (cIFRB) and a control group maintained under standard conditions. We also expanded and cultured adipose tissue-derived mesenchymal stem cells (MSCs) on cIFRB and compared them to standard conditions subjected to a scratch injury to compare survival, proliferation, and wound healing. Results: The wound healing of the cIRFB treatment group was significantly faster than the control group of mice. The wound-healing effect of mesenchymal stem cells on cIRFB was also increased and associated with significant migration to the wound area. Conclusions: Wound healing is improved in a mouse model exposed to cFIRB. The ceramic blanket also promotes survival, proliferation, increased migration, and wound healing of MSCs without affecting their survival and proliferation. The utilization of cFIRB in cellular biology and medical applications may be promising in many situations currently explored in animal and human models. This technology needs no direct or battery power source and is entirely autonomous and noninvasive, making its application possible in any environment.


2021 ◽  
Vol 9 (A) ◽  
pp. 35-41
Author(s):  
Nur Fitriani Hamra ◽  
Agung Putra ◽  
Arya Tjipta ◽  
Nur Dina Amalina ◽  
Taufiqurrachman Nasihun

BACKGROUND: The active myofibroblast producing extracellular matrix deposition regarding wound closure is characterized by alpha-smooth muscle actin (α-SMA) expression. However, the persistence of α-SMA expression due to prolonged inflammation may trigger scar formation. A new strategy to control α-SMA expression in line with wound closure improvement uses hypoxic mesenchymal stem cells (HMSCs) due to their ability to firmly control inflammation for early initiating cell proliferation, including the regulation of α-SMA expression associated with wound closure acceleration. AIM: This study aimed to explore the role of HMSCs in accelerating the optimum wound closure percentages through controlling the α-SMA expression. MATERIALS AND METHODS: Twenty-four full-thickness rats wound model were randomly divided into four groups: Sham (Sh), Control (C) by NaCl administration only, and two treatment groups by HMSCs at doses of 1.5×106 cells (T1) and HMSCs at doses of 3×106 cells (T2). HMSCs were incubated under hypoxic conditions. The α-SMA expression was analyzed under immunohistochemistry staining assay, and the wound closure percentage was analyzed by ImageJ software. RESULTS: This study showed a significant increase in wound closure percentage in all treatment groups that gradually initiated on days 6 and 9 (p < 0.05). In line with the increase of wound closure percentages on day 9, there was also a significant decrease in α-SMA expression in all treatment groups (p < 0.05), indicating the optimum wound healing has preceded. CONCLUSION: HMSCs have a robust ability to accelerated wound closure improvement to the optimum wound healing by controlling α-SMA expression depending on wound healing phases.


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