scholarly journals Human keratinocyte-derived extracellular vesicles activate the MAPKinase pathway and promote cell migration and proliferation in vitro

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Azela Glady ◽  
Arno Vandebroek ◽  
Masato Yasui
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Human Keratinocytes ◽  
Accelerate Wound Healing ◽  
Complex Biological Process ◽  
Cell Migration And Proliferation

Abstract Background Wound healing is a complex biological process and complete skin regeneration is still a critical challenge. Extracellular vesicles (EVs) play essential roles in cell communication and cell regeneration, and recent studies have suggested that EVs may contribute to wound healing, though the molecular mechanisms behind this contribution remain unclear. For these reasons, we decided to use EVs isolated from human keratinocytes (HaCaT) in vitro to determine the potential mechanism of action of EV-derived wound healing. Method Scratch assays were used to determine cell migration and proliferation. Scratched cells were exposed to EVs in multiple conditions to determine how they affect wound healing. Statistical analysis between groups was carried out to using Student’s two-sided t test. A p value of <  0.05 was considered statistically significant. Result We found that proteomic analysis of purified EVs shows enrichment of proteins associated with cell communication and signal transduction, such as MAPK pathways, and keratinocyte and fibroblast cultures exposed to EVs had higher levels of proliferation, migration, and ERK1/2 and P38 activation. Moreover, we found that treatment with specific ERK1/2 and P38 signaling inhibitors PD98059 and SB239063 impaired EV-mediated cell migration, which suggests that ERK1/2 and P38 signaling is essential for EV-induced wound healing. Conclusion HaCaT cell-derived EVs accelerate the migration and proliferation of human keratinocytes and fibroblasts and may promote wound healing via the activation of MAPKinase pathways. These findings may be key in developing new methods to treat wounds and accelerate wound healing in the future.

scholarly journals Microfluidic and Lab-on-a-Chip Systems for Cutaneous Wound Healing Studies

2021 ◽  
Author(s):  
Ghazal Shabestani Monfared ◽  
Peter Ertl ◽  
Mario Rothbauer
Keyword(s):  
Wound Healing ◽  
Molecular Mechanisms ◽  
Chronic Wounds ◽  
Cell Communication ◽  
Lab On A Chip ◽  
Tissue Level ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound

Cutaneous wound healing is a complex multi-stage process involving direct and indirect cell communication events with the aim of efficiently restoring the barrier function of the skin. One key aspect in cutaneous wound healing is associated with cell movement and migration into the physically, chemically and biologically injured area resulting in wound closure. Understanding the conditions under which cell migration is impaired and elucidating the cellular and molecular mechanisms that improve healing dynamics is therefore crucial in devising novel therapeutic strategies to elevate patient suffering, reduce scaring and eliminate chronic wounds. Following the global trend towards automation, miniaturization and integration of cell-based assays into microphysiological systems, conventional wound healing assays such as the scratch assay or cell exclusion assay have recently been translated and improved using microfluidics and lab-on-a-chip technologies. These miniaturized cell analysis systems allow precise spatial and temporal control over a range of dynamic microenvironmental factors including shear stress, biochemical and oxygen gradients to create more reliable in vitro models that resemble the in vivo microenvironment of a wound more closely on a molecular, cellular, and tissue level. The current review provides (a) an overview on the main molecular and cellular processes that take place during wound healing, (b) a brief introduction into conventional in vitro wound healing assays, and (c) a perspective on future cutaneous and vascular wound healing research using microfluidic technology.

scholarly journals Tiny Actors in the Big Cellular World: Extracellular Vesicles Playing Critical Roles in Cancer

2020 ◽  
Vol 21 (20) ◽  
pp. 7688 ◽  
Author(s):  
Ancuta Jurj ◽  
Cecilia Pop-Bica ◽  
Ondrej Slaby ◽  
Cristina D. Ştefan ◽  
William C. Cho ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Recipient Cell ◽  
Cell Communication ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Cellular Functions ◽  
Membrane Bound

Communications among cells can be achieved either via direct interactions or via secretion of soluble factors. The emergence of extracellular vesicles (EVs) as entities that play key roles in cell-to-cell communication offer opportunities in exploring their features for use in therapeutics; i.e., management and treatment of various pathologies, such as those used for cancer. The potential use of EVs as therapeutic agents is attributed not only for their cell membrane-bound components, but also for their cargos, mostly bioactive molecules, wherein the former regulate interactions with a recipient cell while the latter trigger cellular functions/molecular mechanisms of a recipient cell. In this article, we highlight the involvement of EVs in hallmarks of a cancer cell, particularly focusing on those molecular processes that are influenced by EV cargos. Moreover, we explored the roles of RNA species and proteins carried by EVs in eliciting drug resistance phenotypes. Interestingly, engineered EVs have been investigated and proposed as therapeutic agents in various in vivo and in vitro studies, as well as in several clinical trials.

scholarly journals Activator Protein-1 Transcriptional Activity Drives Soluble Micrograft-Mediated Cell Migration and Promotes the Matrix Remodeling Machinery

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Martina Balli ◽  
Jonathan Sai-Hong Chui ◽  
Paraskevi Athanasouli ◽  
Willy Antoni Abreu de Oliveira ◽  
Youssef El Laithy ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Wound Repair ◽  
Molecular Mechanisms ◽  
Cell Model ◽  
Matrix Remodeling ◽  
Activator Protein 1 ◽  
Impaired Wound Healing ◽  
Beneficial Effects

Impaired wound healing and tissue regeneration have severe consequences on the patient’s quality of life. Micrograft therapies are emerging as promising and affordable alternatives to improve skin regeneration by enhancing the endogenous wound repair processes. However, the molecular mechanisms underpinning the beneficial effects of the micrograft treatments remain largely unknown. In this study, we identified the active protein-1 (AP-1) member Fos-related antigen-1 (Fra-1) to play a central role in the extracellular signal-regulated kinase- (ERK-) mediated enhanced cell migratory capacity of soluble micrograft-treated mouse adult fibroblasts and in the human keratinocyte cell model. Accordingly, we show that increased micrograft-dependent in vitro cell migration and matrix metalloprotease activity is abolished upon inhibition of AP-1. Furthermore, soluble micrograft treatment leads to increased expression and posttranslational phosphorylation of Fra-1 and c-Jun, resulting in the upregulation of wound healing-associated genes mainly involved in the regulation of cell migration. Collectively, our work provides insights into the molecular mechanisms behind the cell-free micrograft treatment, which might contribute to future advances in wound repair therapies.

scholarly journals Promotion of Keratinocyte Proliferation by Tracheloside through ERK1/2 Stimulation

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
JaeGoo Kim ◽  
Yu-Kyong Shin ◽  
Ki-Young Kim
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Positive Control ◽  
Skin Injury ◽  
Scratch Assay ◽  
Keratinocyte Proliferation ◽  
Promote Cell Migration ◽  
A Cell ◽  
Cell Migration And Proliferation

Cell migration and proliferation are important for proper wound healing after skin injury. Recent studies have shown that compounds from plants could promote cell migration and proliferation. Tracheloside, which is a plant lignan, has been found to promote the growth of HaCaT cells over 40% compared to other compounds tested based on a cell proliferation assay. An in vitro scratch assay confirmed the healing activity of tracheloside (more than 2-fold increased healing activity after 24 hours of treatment compared with the control) and revealed that this activity is better than that of allantoin (1.2-fold increased after 24 hours of treatment compared with the control), a positive control. With western blot results, wound healing with tracheloside occurred through the phosphorylation of ERK1/2. Therefore, tracheloside is a good candidate to promote wound healing and could be developed as a therapeutic agent for wound treatment or used as a leading compound with higher activity.

scholarly journals Microfluidic and Lab-on-a-Chip Systems for Cutaneous Wound Healing Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 793
Author(s):  
Ghazal Shabestani Monfared ◽  
Peter Ertl ◽  
Mario Rothbauer
Keyword(s):  
Wound Healing ◽  
Molecular Mechanisms ◽  
Chronic Wounds ◽  
Cell Communication ◽  
Lab On A Chip ◽  
Tissue Level ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound

Cutaneous wound healing is a complex, multi-stage process involving direct and indirect cell communication events with the aim of efficiently restoring the barrier function of the skin. One key aspect in cutaneous wound healing is associated with cell movement and migration into the physically, chemically, and biologically injured area, resulting in wound closure. Understanding the conditions under which cell migration is impaired and elucidating the cellular and molecular mechanisms that improve healing dynamics are therefore crucial in devising novel therapeutic strategies to elevate patient suffering, reduce scaring, and eliminate chronic wounds. Following the global trend towards the automation, miniaturization, and integration of cell-based assays into microphysiological systems, conventional wound healing assays such as the scratch assay and cell exclusion assay have recently been translated and improved using microfluidics and lab-on-a-chip technologies. These miniaturized cell analysis systems allow for precise spatial and temporal control over a range of dynamic microenvironmental factors including shear stress, biochemical and oxygen gradients to create more reliable in vitro models that resemble the in vivo microenvironment of a wound more closely on a molecular, cellular, and tissue level. The current review provides (a) an overview on the main molecular and cellular processes that take place during wound healing, (b) a brief introduction into conventional in vitro wound healing assays, and (c) a perspective on future cutaneous and vascular wound healing research using microfluidic technology.

The role of fructose-1, 6-diphosphate in cell migration and proliferation in an in vitro xenograft blood vessel model of vascular wound healing

1999 ◽  
Vol 35 (9) ◽  
pp. 510-514 ◽  
Author(s):  
Hari H. P. Cohly ◽  
James W. Stephens ◽  
Michael F. Angel ◽  
James C. Johnson ◽  
Angel K. Markov
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Blood Vessel ◽  
Cell Migration And Proliferation

THE ROLE OF FDP IN CELL MIGRATION AND PROLIFERATION IN AN IN-VITRO XENOGRAFT BLOOD VESSEL MODEL OF VASCULAR WOUND HEALING

1998 ◽  
Vol 91 (Supplement) ◽  
pp. S14
Author(s):  
James W. Stephens ◽  
Had H. P. Cohly ◽  
Michael F. Angel ◽  
Angel K. Markov
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Blood Vessel ◽  
Cell Migration And Proliferation

scholarly journals Extracellular Vesicle Influence on Wound Healing

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A413-A413
Author(s):  
Erica C Visentin ◽  
Robert E Pogue ◽  
Thiago Rosa ◽  
Brenda Marra
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Extracellular Vesicles ◽  
International Society ◽  
Diabetic Foot ◽  
Cell Biology ◽  
Healing Process ◽  
International Diabetes Federation ◽  
Vitro Assay

Abstract Diabetes is a highly prevalent disease in the world and it is involved in several chronic complications, such retinopathy, nephropathy, neuropathy, cardiovascular disease and the diabetic foot. Up to 28% of diabetic foot ulcers result in some form of amputation that lead to reduced productive activity and quality of life, as well as increased social costs. Advance in the understanding of the healing process changes in diabetic individuals is fundamental to improve diabetic foot care. Extracellular vesicles are intercellular communication agents that influence physiological and pathological processes. The objective of this research was to examine the influence of extracellular vesicles collected of diabetic individuals on cell proliferation, viability and migration in wounds. The procedures included in vitro assay of migration, senescence, cellular viability and oxide nitric production. Extracellular vesicles have been shown to stimulate the cell migration process and this function was not poorly influenced by metabolic control. References: 1. International Diabetes Federation. Diabetes Atlas, 2019. www.diabetesatlas.org. 2. Than UTT, Guanzon D, Leavesley D, Parker T. Association of Extracellular Membrane Vesicles with Cutaneous Wound Healing. Int J Mol Sci. 2017;18(5):956. 3. Van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213–228. 4. Lampugnani MG. Cell migration into a wounded area in vitro. Methods Mol Biol. 1999;96:177–182.5. Sociedade Brasileira de Diabetes. Diretrizes da Sociedade de Diabetes 2017–2018. ISBN: 978-85-93746-02-4. São Paulo: Editora Clannad, 2017.6. Sociedade Brasileira de Cardiologia. Atualização da Diretrizes da Sociedade de Dislipidemia e Prevenção da Aterosclerose - 2017. ISBN: 0066-783X, vol 109, nº2, supl 1, agosto, 2017.7. Leroyer AS, Tedgui A, Boulanger CM. Microparticles and type 2 diabetes. Diabetes Metab. 2008;34 Suppl 1:S27-S32.8. International Society for Extracellular Vesicles. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. Journal of Extracellular Vesicles, 7:1, 2018.9. Deng F, Wang S, Zhang L. Endothelial Microparticles Act as Novel Diagnostic and Therapeutic Biomarkers of Diabetes and Its Complications: A Literature Review. Biomed Res Int. 2016;2016:9802026.

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