PTEN Inhibition Accelerates Corneal Endothelial Wound Healing through Increased Endothelial Cell Division and Migration

Background. When vascular endothelial cells are subjected to external stimuli, paracrine hormones and cytokines act on adjacent cells. The regulation of the biological behaviour of cells is closely related to the maintenance of organ function and the occurrence and development of disease. However, it is unclear whether vascular endothelial cells affect the biological behaviour of cells involved in wound repair through autocrine and paracrine mechanisms and ultimately play a role in wound healing. We aimed to verify the effect of the autocrine and paracrine functions of vascular endothelial cells on wound healing. Materials and Methods. ELISA was used to detect platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor in human umbilical vascular endothelial cell-conditioned medium (HUVEC-CM). Different concentrations of HUVEC-CM were used to treat different stem cells. CCK-8 and scratch assays were used to detect the proliferation and migration ability of each cell. A full-thickness dorsal skin defect model was established in mice, and skin wound healing was observed after the local injection of HUVEC-CM, endothelial cell medium (ECM), or normal saline. H&E staining and immunofluorescence were used to observe the gross morphology of the wound tissue, the epithelial cell migration distance, and the expression of CD3 and CD31. Results. HUVEC-CM promotes the proliferation and migration of epidermal stem cells, skin fibroblasts, bone marrow mesenchymal stem cells, and HUVECs themselves. Furthermore, HUVEC-CM can promote angiogenesis in mouse skin wounds and granulation tissue formation and can accelerate wound surface epithelialization and collagen synthesis, thereby promoting wound healing. Conclusion. Our results clearly suggest that it is practicable and effective to promote wound healing with cytokines secreted by vascular endothelial cells in a mouse model.

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An in vitro model for investigation of vitamin A effects on wound healing

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000692 ◽

2021 ◽

pp. 1-6

Author(s):

Hoda Keshmiri Neghab ◽

Mohammad Hasan Soheilifar ◽

Gholamreza Esmaeeli Djavid

Keyword(s):

Wound Healing ◽

Endothelial Cell ◽

Vitamin A ◽

In Vitro Model ◽

Cellular Proliferation ◽

Endothelial Cell Migration ◽

Normal Fibroblast ◽

Anti Inflammatory ◽

Vitro Model

Abstract. Wound healing consists of a series of highly orderly overlapping processes characterized by hemostasis, inflammation, proliferation, and remodeling. Prolongation or interruption in each phase can lead to delayed wound healing or a non-healing chronic wound. Vitamin A is a crucial nutrient that is most beneficial for the health of the skin. The present study was undertaken to determine the effect of vitamin A on regeneration, angiogenesis, and inflammation characteristics in an in vitro model system during wound healing. For this purpose, mouse skin normal fibroblast (L929), human umbilical vein endothelial cell (HUVEC), and monocyte/macrophage-like cell line (RAW 264.7) were considered to evaluate proliferation, angiogenesis, and anti-inﬂammatory responses, respectively. Vitamin A (0.1–5 μM) increased cellular proliferation of L929 and HUVEC (p < 0.05). Similarly, it stimulated angiogenesis by promoting endothelial cell migration up to approximately 4 fold and interestingly tube formation up to 8.5 fold (p < 0.01). Furthermore, vitamin A treatment was shown to decrease the level of nitric oxide production in a dose-dependent effect (p < 0.05), exhibiting the anti-inflammatory property of vitamin A in accelerating wound healing. These results may reveal the therapeutic potential of vitamin A in diabetic wound healing by stimulating regeneration, angiogenesis, and anti-inﬂammation responses.

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Faculty Opinions recommendation of HLA class I molecules partner with integrin β4 to stimulate endothelial cell proliferation and migration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.7711957.8463067 ◽

2011 ◽

Author(s):

Arthur Mercurio

Keyword(s):

Cell Proliferation ◽

Endothelial Cell ◽

Hla Class I ◽

Class I ◽

Endothelial Cell Proliferation ◽

Cell Proliferation And Migration ◽

Hla Class I Molecules ◽

Integrin Β4 ◽

And Migration ◽

Proliferation And Migration

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Wound With Diabetes: Present Scenario And Future

Current Diabetes Reviews ◽

10.2174/1573399816666200703180137 ◽

2020 ◽

Vol 16 ◽

Author(s):

Kuldeep B. Pawar ◽

Shivani Desai ◽

Ramesh R. Bhonde ◽

Ritesh P. Bhole ◽

Atul A. Deshmukh

Keyword(s):

Wound Healing ◽

Blood Flow ◽

Healing Process ◽

Endocrine System ◽

Healing Time ◽

Special Focus ◽

Diabetic Wound ◽

Management Options ◽

And Migration ◽

Proliferation And Migration

: Diabetes is a chronic metabolic disorder of endocrine system characterized by increase in blood glucose level. Several factors such as pancreatic damage, oxidative stress, infection, genetic factor, obesity, liver dysfunction play a vital role in pathogenesis of diabetes which further lead to serious diabetic complications. Diabetic wound is one such complication where the wound formation occurs, especially due to pressure and its healing process is disrupted due to factors such as hyperglycemia, neuropathy, nephropathy, peripheral vascular disease, reduction of blood flow, atherosclerosis, impaired fibroblast. Process of wound healing is delayed due to different abnormalities like alteration in nitric oxide level, increase in aldose reductase, sorbitol and fructose. Therefore, diabetic wound requires more time to heal as compare to normal wound. Healing time is delayed in diabetic wound due to many factors such as stress, decreased oxygenation supply, infection, decreased blood flow, impaired proliferation and migration rate, impaired growth factor production, impaired keratinocytes proliferation and migration, and altered vascular endothelial mediators. The current treatment for diabetic wound includes wound patches, oxygenation therapy, hydrogel patches, gene therapy, laser therapy, and stem cell therapy. Medications with phytoconstituents is also one way to manage diabetic wound, but it is not more effective for quick healing. The objective of this review is to understand the potential of various management options which are available for diabetic wound, with a special focus on biological cells.

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Bioinformatics-based approach for identifying peptide inhibitors of endothelial cell proliferation and migration

Science-Business eXchange ◽

10.1038/scibx.2008.788 ◽

2008 ◽

Vol 1 (32) ◽

pp. 788-788

Keyword(s):

Cell Proliferation ◽

Endothelial Cell ◽

Peptide Inhibitors ◽

Endothelial Cell Proliferation ◽

Cell Proliferation And Migration ◽

And Migration ◽

Proliferation And Migration

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Wound Healing Promotion by Hyaluronic Acid: Effect of Molecular Weight on Gene Expression and In Vivo Wound Closure

Pharmaceuticals ◽

10.3390/ph14040301 ◽

2021 ◽

Vol 14 (4) ◽

pp. 301

Author(s):

Yayoi Kawano ◽

Viorica Patrulea ◽

Emmanuelle Sublet ◽

Gerrit Borchard ◽

Takuya Iyoda ◽

...

Keyword(s):

Gene Expression ◽

Molecular Weight ◽

Wound Healing ◽

Hyaluronic Acid ◽

Healing Process ◽

Dermal Fibroblasts ◽

Water Soluble ◽

Wound Healing Process ◽

And Migration ◽

Proliferation And Migration

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.

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Conditioned medium from the human umbilical cord-mesenchymal stem cells stimulate the proliferation of human keratinocytes

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2019-0283 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Sushmitha Sriramulu ◽

Antara Banerjee ◽

Ganesan Jothimani ◽

Surajit Pathak

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Conditioned Medium ◽

Umbilical Cord ◽

Human Keratinocytes ◽

Human Umbilical Cord ◽

Hacat Cells ◽

And Migration

AbstractObjectivesWound healing is a complex process with a sequence of restoring and inhibition events such as cell proliferation, differentiation, migration as well as adhesion. Mesenchymal stem cells (MSC) derived conditioned medium (CM) has potent therapeutic functions and promotes cell proliferation, anti-oxidant, immunosuppressive, and anti-apoptotic effects. The main aim of this research is to study the role of human umbilical cord-mesenchymal stem cells (UC-MSCs) derived CM in stimulating the proliferation of human keratinocytes (HaCaT).MethodsFirstly, MSC were isolated from human umbilical cords (UC) and the cells were then cultured in proliferative medium. We prepared and collected the CM after 72 h. Morphological changes were observed after the treatment of HaCaT cells with CM. To validate the findings, proliferation rate, clonal efficiency and also gene expression studies were performed.ResultsIncreased proliferation rate was observed and confirmed with the expression of Proliferating Cell Nuclear Antigen (PCNA) after treatment with HaCaT cells. Cell-cell strap formation was also observed when HaCaT cells were treated with CM for a period of 5–6 days which was confirmed by the increased expression of Collagen Type 1 Alpha 1 chain (Col1A1).ConclusionsOur results from present study depicts that the secretory components in the CM might play a significant role by interacting with keratinocytes to promote proliferation and migration. Thus, the CM stimulates cellular proliferation, epithelialization and migration of skin cells which might be the future promising application in wound healing.

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Hyaluronan (HA) Immobilized on Surfaces via Self-Assembled Monolayers of HA-Binding Peptide Modulates Endothelial Cell Spreading and Migration through Focal Adhesion

ACS Applied Materials & Interfaces ◽

10.1021/acsami.1c05574 ◽

2021 ◽

Author(s):

Xinqing Pang ◽

Weiqi Li ◽

Lan Chang ◽

Julien E. Gautrot ◽

Wen Wang ◽

...

Keyword(s):

Endothelial Cell ◽

Focal Adhesion ◽

Cell Spreading ◽

Self Assembled Monolayers ◽

Binding Peptide ◽

Assembled Monolayers ◽

Self Assembled ◽

And Migration

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Migration and Proliferation Effects of Thymoquinone-Loaded Nanostructured Lipid Carrier (TQ-NLC) and Thymoquinone (TQ) on In Vitro Wound Healing Models

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/9725738 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 1

Author(s):

Henna Roshini Alexander ◽

Sharifah Sakinah Syed Alwi ◽

Latifah Saiful Yazan ◽

Fatin Hanani Zakarial Ansar ◽

Yong Sze Ong

Keyword(s):

Wound Healing ◽

Nigella Sativa ◽

Drug Carrier ◽

Healing Process ◽

Diabetic Patients ◽

Nanostructured Lipid Carrier ◽

Impaired Wound Healing ◽

And Migration ◽

Proliferation And Migration

Wound healing is a regulated biological event that involves several processes including infiltrating leukocyte subtypes and resident cells. Impaired wound healing is one of the major problems in diabetic patients due to the abnormal physiological changes of tissues and cells in major processes. Thymoquinone, a bioactive compound found in Nigella sativa has been demonstrated to possess antidiabetic, anti-inflammatory, and antioxidant effects. Today, the rapidly progressing nanotechnology sets a new alternative carrier to enhance and favour the speed of healing process. In order to overcome its low bioavailability, TQ is loaded into a colloidal drug carrier known as a nanostructured lipid carrier (NLC). This study aimed to determine the effect of TQ-NLC and TQ on cell proliferation and migration, mode of cell death, and the antioxidant levels in normal and diabetic cell models, 3T3 and 3T3-L1. Cytotoxicity of TQ-NLC and TQ was determined by MTT assay. The IC10 values obtained for 3T3-L1 treated with TQ-NLC and TQ for 24 hours were 4.7 ± 3.3 and 5.3 ± 0.6 μM, respectively. As for 3T3, the IC10 values obtained for TQ-NLC and TQ at 24 hours were 4.3 ± 0.17 and 3.9 ± 2.05 μM, respectively. TQ-NLC was observed to increase the number of 3T3 and 3T3-L1 healthy cells (87–95%) and gradually decrease early apoptotic cells in time- and dose-dependant manner compared with TQ. In the proliferation and migration assay, 3T3-L1 treated with TQ-NLC showed higher proliferation and migration rate (p<0.05) compared with TQ. TQ-NLC also acted as an antioxidant by reducing the ROS levels in both cells after injury at concentration as low as 3 μM. Thus, this study demonstrated that TQ-NLC has better proliferation and migration as well as antioxidant effect compared with TQ especially on 3T3-L1 which confirms its ability as a good antidiabetic and antioxidant agent.

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