Promising effects of exosomes isolated from menstrual blood‐derived mesenchymal stem cell on wound‐healing process in diabetic mouse model

Background: Diabetes is a disease that affects people worldwide, including in Indonesia. The prevalence of diabetes in Indonesia is increasing from year to year. One of the most devastating complications of diabetes mellitus is diabetic ulcers, which is a limb-threatening complication. Over the past few decades, ozone generated using plasma medical technology has been investigated as an agent that helps wound healing. This study aims to evaluate the effects of topical ozonated virgin coconut oil (VCO) in a diabetic wound mouse model. Methods: This study was an experimental study with a post-test control design. An ulcer wound model was made in 50 diabetic male Wistar mice, divided into five groups, and a control group of 10 non-diabetic mice. The control groups were given conventional therapy only and the treatment groups were also given topical ozonated VCO with different flow durations (0 min, 90 min, 7 h, 14 h). Macroscopic appearance and wound contraction were observed. HSP90β, VEGF-A, EGF, bFGF, and CD34 levels were measured from the immunostained slices of wound margins. Results: The reduction of wound length was proportionally related to the duration of ozone flow. Ozonated VCO with a longer duration of ozone flow healed the wound more quickly and had the shortest wound length. VCO with ozone flow for 14 hours (16837.10 µm) had the biggest reduction in wound length compared to other groups. The wounds treated with ozonated VCO showed an increase in HSP90β, VEGF-A, EGF, bFGF, and CD34 levels that correlated to improved wound healing. A longer period of treatment resulted in higher levels of wound healing biomarkers compared to shorter therapeutic durations. Conclusions: Topical ozonated VCO improved the wound healing process in a diabetic ulcer mouse model by improving macroscopic wound appearance and increasing levels of wound healing biomarkers.

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Topical ozonated virgin coconut oil improves wound healing and increases HSP90α, VEGF-A, EGF, bFGF and CD34 in diabetic ulcer mouse model of wound healing

F1000Research ◽

10.12688/f1000research.22525.1 ◽

2020 ◽

Vol 9 ◽

pp. 580

Author(s):

Renni Yuniati ◽

Prasetyowati Subchan ◽

Wibi Riawan ◽

Matthew Brian Khrisna ◽

Maryam Restiwijaya ◽

...

Keyword(s):

Wound Healing ◽

Mouse Model ◽

Healing Process ◽

Coconut Oil ◽

Control Group ◽

Wound Healing Process ◽

Virgin Coconut Oil ◽

Diabetic Ulcer ◽

Macroscopic Appearance ◽

Wound Length

Background: Diabetes is a disease that affects people worldwide, including in Indonesia. The prevalence of diabetes in Indonesia is increasing from year to year. One of the most devastating complications of diabetes mellitus is diabetic ulcers, which is a limb-threatening complication. Over the past few decades, ozone generated using plasma medical technology has been investigated as an agent that helps wound healing. This study aims to evaluate the effects of topical ozonated virgin coconut oil (VCO) in a diabetic wound mouse model. Methods: This study was an experimental study with a post-test control design. An ulcer wound model was made in 50 diabetic male Wistar mice, divided into five groups, and a control group of 10 non-diabetic mice. The control groups were given conventional therapy only and the treatment groups were also given topical ozonated VCO with different flow durations (0 min, 90 min, 7 h, 14 h). Macroscopic appearance and wound contraction were observed. HSP90β, VEGF-A, EGF, bFGF and CD34 levels were measured from the immunostained slices of wound margins. Results: The reduction of wound length was proportionally related to the duration of ozone flow. Ozonated VCO with a longer duration of ozone flow healed the wound more quickly and had the shortest wound length. VCO with ozone flow for 14 hours (16837.10 µm) had the biggest reduction in wound length compared to other groups. The wounds treated with ozonated VCO showed an increase in HSP90β, VEGF-A, EGF, bFGF and CD34 levels that correlated to improved wound healing. A longer period of treatment resulted in higher levels of wound healing biomarkers compared to shorter therapeutic durations. Conclusions: Topical ozonated VCO improved the wound healing process in a diabetic ulcer mouse model by improving macroscopic wound appearance and increasing levels of wound healing biomarkers.

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Sulfur mustard cutaneous injury characterization based on SKH-1 mouse model: relevance of non-invasive methods in terms of wound healing process analyses

Skin Research and Technology ◽

10.1111/j.1600-0846.2012.00621.x ◽

2012 ◽

Vol 19 (1) ◽

pp. e146-e156 ◽

Cited By ~ 9

Author(s):

Cécile Cléry-Barraud ◽

Nina Nguon ◽

Virginie Vallet ◽

Catherine Sentenac ◽

Elise Four ◽

...

Keyword(s):

Wound Healing ◽

Mouse Model ◽

Sulfur Mustard ◽

Healing Process ◽

Wound Healing Process ◽

Cutaneous Injury ◽

Non Invasive

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Advances of Stem Cell Therapeutics in Cutaneous Wound Healing and Regeneration

Mediators of Inflammation ◽

10.1155/2017/5217967 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 63

Author(s):

Suman Kanji ◽

Hiranmoy Das

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Stem Cell ◽

Wound Repair ◽

Chronic Wounds ◽

Healing Process ◽

Treatment Modalities ◽

Wound Healing Process ◽

Cutaneous Wound Healing ◽

Cutaneous Wound

Cutaneous wound healing is a complex multiple phase process, which overlaps each other, where several growth factors, cytokines, chemokines, and various cells interact in a well-orchestrated manner. However, an imbalance in any of these phases and factors may lead to disruption in harmony of normal wound healing process, resulting in transformation towards chronic nonhealing wounds and abnormal scar formation. Although various therapeutic interventions are available to treat chronic wounds, current wound-care has met with limited success. Progenitor stem cells possess potential therapeutic ability to overcome limitations of the present treatments as it offers accelerated wound repair with tissue regeneration. A substantial number of stem cell therapies for cutaneous wounds are currently under development as a result of encouraging preliminary findings in both preclinical and clinical studies. However, the mechanisms by which these stem cells contribute to the healing process have yet to be elucidated. In this review, we emphasize on the major treatment modalities currently available for the treatment of the wound, role of various interstitial stem cells and exogenous adult stem cells in cutaneous wound healing, and possible mechanisms involved in the healing process.

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Stem Cell-Derived Nanovesicles: A Novel Cell-Free Therapy for Wound Healing

Stem Cells International ◽

10.1155/2021/1285087 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Jianghong Huang ◽

Jun Zhang ◽

Jianyi Xiong ◽

Shuqing Sun ◽

Jiang Xia ◽

...

Keyword(s):

Wound Healing ◽

Stem Cell ◽

Wound Repair ◽

Current Knowledge ◽

Healing Process ◽

Biologically Active ◽

Research Progress ◽

Wound Healing Process ◽

Messenger Rnas ◽

Skin Wound Healing

Wound healing and regeneration are a dynamic and complex process that requires a collaborative effort between growth factors, epidermal cells, dermal cells, extracellular matrix, and vessels local to the wound area. Mesenchymal stem cells participate in the recruitment site, mainly by releasing secretory factors and matrix proteins to promote wound healing. Stem cell-derived nanovesicles (CDNs), including microvesicles, exosomes, and exosome mimetics, contain most of the biologically active substances of their parent cells and have similar effects. CDNs can shuttle various proteins, messenger RNAs, and microRNAs to regulate the activity of receptor cells, and they play important roles in skin wound healing. This article reviews recent research progress on CDNs for wound repair. We summarize current knowledge on how CDNs regulate immunity, fibroblast activity, angiogenesis, and scar formation in the wound healing process. This review can help researchers explore new treatment strategies to enhance the therapeutic efficacy of CDNs, which have a promising future as naturally cell-free therapies.

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The Effects of Cytokines in Adipose Stem Cell-Conditioned Medium on the Migration and Proliferation of Skin FibroblastsIn Vitro

BioMed Research International ◽

10.1155/2013/578479 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 24

Author(s):

Jiajia Zhao ◽

Li Hu ◽

Jiarong Liu ◽

Niya Gong ◽

Lili Chen

Keyword(s):

Wound Healing ◽

Stem Cell ◽

Conditioned Medium ◽

Healing Process ◽

Dermal Fibroblasts ◽

Wound Healing Process ◽

Adipose Stem Cell ◽

And Migration ◽

Cell Conditioned Medium ◽

Proliferation And Migration

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.

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The Key Role of Insulin-Like Growth Factor I in Limbal Stem Cell Differentiation and the Corneal Wound-Healing Process

Stem Cells and Development ◽

10.1089/scd.2012.0180 ◽

2012 ◽

Vol 21 (18) ◽

pp. 3341-3350 ◽

Cited By ~ 43

Author(s):

Peter Trosan ◽

Eliska Svobodova ◽

Milada Chudickova ◽

Magdalena Krulova ◽

Alena Zajicova ◽

...

Keyword(s):

Wound Healing ◽

Stem Cell ◽

Growth Factor ◽

Healing Process ◽

Stem Cell Differentiation ◽

Wound Healing Process ◽

Factor I ◽

Corneal Wound ◽

Limbal Stem Cell

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Pengaruh Gel Ekstrak Daun Kerehau (Callicarpa longifolia Lam.) Terhadap Penyembuhan Luka Pada Model Tikus Diabetes

Kartika Jurnal Ilmiah Farmasi ◽

10.26874/kjif.v6i2.154 ◽

2019 ◽

Vol 6 (2) ◽

pp. 70

Author(s):

Sansan Candra ◽

Elis Susilawati ◽

I Ketut Adnyana

Keyword(s):

Wound Healing ◽

Mouse Models ◽

Leaf Extract ◽

Healing Process ◽

Diabetic Mouse ◽

Diabetic Animal ◽

Wound Healing Process ◽

Diabetic Ulcer ◽

Average Percentage ◽

Accelerate Wound Healing

Abstrak Luka diabetes adalah infeksi, luka dan destruksi pada penderita diabetes melitus. Daun kerehau secara empiris digunakan oleh suku Dayak Tunjung sebagai obat luka dan bengkak. Penelitian ini bertujuan untuk mengetahui pengaruh gel ekstrak daun kerehau terhadap penyembuhan luka pada model tikus diabetes. Induksi diabetes dilakukan menggunakan aloksan dosis 75 mg/kg BB intravena. Model hewan diabetes dibuat luka dengan kedalaman 0,3 cm menggunakan scalpel steril pada bagian punggung. Hewan uji dibagi menjadi lima kelompok dan mendapatkan sediaan basis gel, Prontosan® gel, sediaan gel ekstrak daun kerehau konsentrasi 2,5%, 5%, dan 10%. Pengolesan gel dilakukan dua kali sehari selama 13 hari. Parameter penyembuhan luka dilakukan dengan mengukur panjang luka dan dinyatakan dengan persentase penyembuhan luka. Hasil pengujian menunjukkan bahwa dengan pemberian gel ekstrak daun kerehau dapat mempercepat penyembuhan luka pada model tikus diabetes dimana sediaan gel ekstrak daun kerehau konsentrasi 2,5% memberikan kesembuhan pada hari ke-13, sediaan gel konsentrasi 5% pada hari ke-12, dan sediaan gel konsentrasi 10% pada hari ke-9. Hasil juga menunjukkan rata-rata persentase penyembuhan luka pada kelompok konsentrasi 10% lebih tinggi dibandingkan konsentrasi 2,5% dan 5%. Dapat disimpulkan bahwa pemberian gel ekstrak daun kerehau dapat menyembuhkan luka pada model tikus diabetes. Kata kunci: Luka diabetes, daun kerehau, penyembuhan luka Effect of Kerehau Leaves Extract Gel to Wound Healing Process in Diabet Rats Model Abstract Diabetic wounds are infection, injury and destruction in people with diabetes mellitus. Kauhau leaves are empirically used by the Tunjung Dayak tribe as a medicine for wounds and swelling. The aim of this study was to determine the effect of Kerehau leaf extract gel on wound healing in diabetic mouse models. Induction of diabetes is done using alloxan dose of 75 mg / kg BW intravenously. The diabetic animal model was made with a 0.3 cm depth wound using a sterile scalpel on the back. The test animals were divided into five groups and obtained base gel preparations, Prontosan® gel, preparations of Kerehau leaf extract gel concentrations of 2.5%, 5%, and 10%. Gel application is done twice a day for 13 days. Wound healing parameters were performed by measuring the length of the wound and expressed by the percentage of wound healing. The test results showed that administration of Kerehau leaf extract gel could accelerate wound healing in diabetic mouse models where the preparations of Kerehau leaf extract gel with a concentration of 2.5% gave healing on the 13th day, preparations for 5% gel on 12th day, and preparations gel concentration of 10% on day 9. The results also showed that the average percentage of wound healing in the concentration group was 10% higher than the concentration of 2.5% and 5%. It can be concluded that administration of Kerehau leaf extract gel can heal wounds in diabetic mouse models. Keywords: Diabetic ulcer, kerehau leaf, wound healing

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FOXN1 Transcription Factor in Epithelial Growth and Wound Healing

Molecular and Cellular Biology ◽

10.1128/mcb.00110-17 ◽

2017 ◽

Vol 37 (17) ◽

Cited By ~ 2

Author(s):

Anna I. Grabowska ◽

Tomasz Wilanowski

Keyword(s):

Wound Healing ◽

Transcription Factor ◽

Stem Cell ◽

Stem Cell Niche ◽

Healing Process ◽

Skin Wound ◽

Wound Healing Process ◽

Skin Wound Healing ◽

Important Player ◽

Cell Niche

ABSTRACT FOXN1 is a prodifferentiation transcription factor in the skin epithelium. Recently, it has also emerged as an important player in controlling the skin wound healing process, as it actively participates in reepithelialization and is thought to be responsible for scar formation. FOXN1 positivity is also a feature of pigmented keratinocytes, including nevi, and FOXN1 is an attribute of benign epithelial tumors. The lack of FOXN1 favors the skin regeneration process displayed by nude mice, pointing to FOXN1 as a switch between regeneration and reparative processes. The stem cell niche provides a functional source of cells after the loss of tissue following wounding. The involvement of prodifferentiation factors in the regulation of this pool of stem cells is suggested. However, the exact mechanism is still under question, and we speculate that the FOXN1 transcription factor is involved in this process. This review analyzes the pleiotropic effects of FOXN1 in the skin, its function in the tumorigenesis process, and its potential role in depletion of the stem cell niche after injury, as well as its suggested mechanistic role, acting in a cell-autonomous and a non-cell-autonomous manner during skin self-renewal.

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