TNF-α-Activated MSC-CM Topical Gel Effective in Increasing PDGF Level, Fibroblast Density, and Wound Healing Process Compared to Subcutaneous Injection Combination

Kuntardjo, Novalia; Dharmana, Edi; Chodidjah, Chodidjah; Nasihun, Taufiq R; Putra, Agung

doi:10.15395/mkb.v51n1.1479

Cited by 5 publications

(11 citation statements)

References 19 publications

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“…Therefore, the one primary strategy to accelerate the optimum wound healing without scar formation is by effectively controlling the α-SMA expression using HMSCs treatment. The HMSCs are the most promising therapeutic to control several fibrosis diseases, including scar formation, due to their ability to firmly control the prolonged inflammation for early initiating cell proliferation leading to the optimum wound healing acceleration [23], [32].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Mesenchymal Stem Cells Accelerate Wound Closure Improvement by Controlling α-smooth Muscle actin Expression in the Full-thickness Animal Model

Hamra

Putra

Tjipta

et al. 2021

Open Access Maced J Med Sci

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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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Section: Discussionmentioning

confidence: 99%

Hypoxia Mesenchymal Stem Cells Accelerate Wound Closure Improvement by Controlling α-smooth Muscle actin Expression in the Full-thickness Animal Model

Hamra

Putra

Tjipta

et al. 2021

Open Access Maced J Med Sci

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“…Twenty-four wistar rat (four to six-month old, male, body weight 250-300 grams) were obtained from local farmer at the Java Rat Labs, Tembalang, Semarang, Indonesia. The full-thickness wound model was generated as described previously (Kuntardjo, et al, 2019). In brief, after the hair removal from the dorsal surface and anaesthesiae 6-mm full-thickness skin wounds were created on one side of the midline.…”

Section: The Induction Of Full-thickness Wound Modelmentioning

confidence: 99%

“…The full-thickness rats lubricated with different doses of HMSCs-CM in topical gel. The control groups were lubricated with basis of gel, whereas the treatment groups (T1 and T2) received the gel of HMSCs-CM 200 µL and 400 µL, respectively (Kuntardjo, et al, 2019). The gel was applied for control and treatment groups one doses on the day of induction of the full-thickness wound.…”

Section: Hmscs-cm Treatment To Full-thickness Wound Modelmentioning

confidence: 99%

The Role of Hypoxic Mesenchymal Stem Cells Conditioned Medium in Increasing Vascular Endothelial Growth Factors (VEGF) Levels and Collagen Synthesis to Accelerate Wound Healing

Sunarto

Trisnadi

Putra

et al. 2020

Indones J Cancer Chemoprevent

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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

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“…7 Preconditioning culture in a hypoxic environment is a procedure to improve the quality of MSCs.3 In wound healing, roles of secretome MSC hypoxia using a topical gel have been shown to be more effective. 8 The effect of giving secretome MSC hypoxia in wound healing requires further research.…”

Section: Introductionmentioning

confidence: 99%

“…12 According to research using topical subcutaneous injection of MSC-CM, compared with topical gel MSC-CM worked better on day 6, it was found that the topical group had significantly higher levels of PDGF and fibroblast density on day 6 of wound healing. 8 MSCs can also reduce inflammation, and burn scar formation, and have been shown in preclinical trials to accelerate the healing of acute burn wounds. 13 Other studies at TNF-α concentrations of 5 and 10 ng/mL significantly increased TGF-β and IL-10 levels.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Topical Gel Secretome Hypoxia Mesenchymal Stem Cells (SH-MSCs) on TGF-Β and IL-6 Gene Expression in Wistar Rats Excision Wound Models

arosa

2023

IJMRA

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Wounds on the skin result in damage to the epithelial tissue and skin structure, hampering wound healing and causing acute wounds to become chronic. Secretome Hypoxia Mesenchymal Stem Cells are capable of secretes cytokines and growth factors, including TGF-β which are useful for wound healing. IL-6 is a pro-inflammatory cytokine that is produced in infectious lesions and is also important in wound closure. The aim of the research was to prove the effect of topical SH-MSCs gel on TGF-β and IL-6 gene expression in male Wistar rats with an excision wound model. This study aims to prove the effect of topical gel administration secretome Hypoxia Mesenchymal Stem Cell (SH-MSCs) on TGF-β and IL-6 gene expression in male Wistar rats with an excision wound model. This study is Experimental research with Post-test Only Control Group Design. The number of samples was 18 male Wistar rats with the excision wound model divided into three groups, Group I (K-) was given a basic gel placebo, Group 2 (K+) was given a Clobetasol dose of 0.25g/kg, and Group 3 (P1) was given SH-MSCs gel at a dose of 400 μl/kg BW, treatment for 5 days, on day 6 the skin tissue was examined by RT-PCR to see the expression of the TGF-β and IL-6 genes analyzed by One Way Anova test, continued by Post Hoc LSD test. The average TGF-β gene expression in the P1 group was the highest (1.38) and the mean IL-6 gene expression in the P1 group was the lowest (0.72). One Way Anova test result showed a significant difference in TGF-β gene expression with a value of p=0.056 (p<0.05) and IL-6 p=0.47 (p<0.05). Post Hoc LSD test result on TGF-β gene expression shows that administration of 400μl/kg BW SH-MSCs can increase TGF-β gene expression and reduce IL-6 expression in Wistar rats with an excision wound model. The administration of topical gel SH-MSCs dose of 400 μl/kg BW was proven to significantly increase TGF-β levels in male Wistar rat excision wound model. The administration of topical SH MSCs dose of 400 μl/kg BW can reduce IL-6 levels in male Wistar rat excision wound models.

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TNF-α-Activated MSC-CM Topical Gel Effective in Increasing PDGF Level, Fibroblast Density, and Wound Healing Process Compared to Subcutaneous Injection Combination

Cited by 5 publications

References 19 publications

Hypoxia Mesenchymal Stem Cells Accelerate Wound Closure Improvement by Controlling α-smooth Muscle actin Expression in the Full-thickness Animal Model

Hypoxia Mesenchymal Stem Cells Accelerate Wound Closure Improvement by Controlling α-smooth Muscle actin Expression in the Full-thickness Animal Model

The Role of Hypoxic Mesenchymal Stem Cells Conditioned Medium in Increasing Vascular Endothelial Growth Factors (VEGF) Levels and Collagen Synthesis to Accelerate Wound Healing

The Effect of Topical Gel Secretome Hypoxia Mesenchymal Stem Cells (SH-MSCs) on TGF-Β and IL-6 Gene Expression in Wistar Rats Excision Wound Models

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