scholarly journals Mesenchymal Stem Cells Promote Diabetic Corneal Epithelial Wound Healing Through TSG-6–Dependent Stem Cell Activation and Macrophage Switch

2017 ◽  
Vol 58 (10) ◽  
pp. 4344 ◽  
Author(s):  
Guohu Di ◽  
Xianli Du ◽  
Xia Qi ◽  
Xiaowen Zhao ◽  
Haoyun Duan ◽  
...  
2021 ◽  
Author(s):  
Xuran Li ◽  
Xiaolong Liu ◽  
Yanyan Zhang ◽  
Zhiyu Liu ◽  
Xinyue Li ◽  
...  

Abstract BackgroundRapid restoration of corneal epithelium integrity after injury is particularly important for preserving corneal transparency and vision. Mesenchymal stem cells (MSCs) can be taken into account as the promising regenerative therapeutics for improvement of wound healing processes based on the variety of the effective components. The extracellular vesicles form MSCs, especially exosomes, has been considered as important paracrine mediators though transferring microRNAs into recipient cell. This study investigated the mechanism of human umbilical cord MSC-derived exosomes (HUMSC-exosomes) on corneal epithelial wound healing.MethodsExosomes extracted from HUMSCs were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Corneal fluorescein staining and histological staining were evaluated in a corneal mechanical wound model. Changes in HCECs proliferation after HUMSC-exosomes or miR-21 mimic treatment were evaluated by CCK-8 and EdU assays, while migration was assessed by in vitro scratch wound assay. Full-length transcriptome sequencing was performed to identify the differentially expressed genes associated with HUMSC-exosomes treatment, followed by validation via real-time PCR and Western blot.ResultsThe exosomes derived from HUMSCs can significantly promote corneal epithelial cells proliferation, migration in vitro and accelerate corneal epithelial wound healing in vivo. Similar effects were obtained after miR-21 transfection, while the beneficial effects of HUMSC-exosomes were partially negated by miR-21 knockdown. Results also show that the benefits are associated with decreased PTEN level and activated the PI3K/Akt signaling pathway in HCECs.ConclusionsHUMSC-exosomes could accelerate the recovery of corneal epithelial wounds though restraining PTEN by transferring miR-21, and may represent a promising novel therapeutic agent for corneal wound repair.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Dajeong Yoon ◽  
Dogeon Yoon ◽  
Heejoong Sim ◽  
Inseok Hwang ◽  
Ji-Seon Lee ◽  
...  

Fibroblasts synthesize and secrete dermal collagen, matrix proteins, growth factors, and cytokines. These characteristics of fibroblasts provide a potential way for fibroblast therapy to treat skin ulcers more effectively than conventional therapies such as cytokine therapy and negative pressure wound therapy. However, the obstacle to the commercialization of fibroblast therapy is the limited supply of cells with consistent quality. In this study, we tested whether human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) could be differentiated into fibroblasts considering that they have characteristics of high differentiation rates, unlimited proliferation possibility from a single colony, and homogeneity. As a result, hESC-MSC-derived fibroblasts (hESC-MSC-Fbs) showed a significant increase in the expression of type I and III collagen, fibronectin, and fibroblast-specific protein-1 (FSP-1). Besides, vessel formation and wound healing were enhanced in hESC-MSC-Fb-treated skin tissues compared to PBS- or hESC-MSC-treated skin tissues, along with decreased IL-6 expression at 4 days after the formation of pressure ulcer wound in a mouse model. In view of the limited available cell sources for fibroblast therapy, hESC-MSC-Fbs show a promising potential as a commercial cell therapy source to treat skin ulcers.


2020 ◽  
Vol 56 (20) ◽  
pp. 3043-3046 ◽  
Author(s):  
Swati Sharma ◽  
Chirag Kulkarni ◽  
Manish M. Kulkarni ◽  
Rafat Ali ◽  
Konica Porwal ◽  
...  

We demonstrate the ability of two tripeptides to promote proliferation and modulate the mechanical properties of human mesenchymal stem cells (hMSCs).


2021 ◽  
Vol 14 (2) ◽  
pp. 179-185
Author(s):  
Guo-Hu Di ◽  
◽  
Jing Xu ◽  
Chao-Qun Yu ◽  
Qi-Long Cao ◽  
...  

AIM: To explore the secretome efficacy in tumor necrosis factor (TNF)-α stimulated mouse mesenchymal stem cells (MSCs) in a murine model of corneal limbal alkali injury. METHODS: Corneal limbal stem cell deficiency (LSCD) was created in the eyes of male C57 mice. Concentrated conditioned medium from TNF-α stimulated MSCs (MSC-CMT) was applied topically for 4wk, with basal medium and conditioned medium from MSCs as controls. Corneal opacification, corneal inflammatory response, and corneal neovascularization (NV) were evaluated. Corneal epithelial cell apoptosis, corneal conjunctivation, and inflammatory cell infiltration were assessed with TUNEL staining, CK3 and Muc-5AC immunostaining, and CD11b immunofluorescence staining, respectively. The effect of TSG-6 was further evaluated by knockdown with short hairpin RNA (shRNA). RESULTS: Compared to the controls, topical administration of MSC-CMT significantly ameliorated the clinical symptoms of alkali-induced LSCD, with restrained corneal NV, reduced corneal epithelial cell apoptosis, and inhibition of corneal conjunctivation. In addition, MSC-CMT treatment significantly reduced CD11b+ inflammatory cell infiltration, and inhibited the expression of pro-inflammatory cytokines (IL-1β, TNF-α and IL-6). Furthermore, the promotion of corneal epithelial reconstruction by MSC-CMT was largely abolished by TSG-6 knockdown. CONCLUSION: Our study provides evidence that MSC-CMT enhances the alleviation of corneal alkali injuries, partially through TSG-6-mediated anti-inflammatory protective mechanisms. MSC-CMT may serve as a potential strategy for treating corneal disorders.


2020 ◽  
Vol 15 (3) ◽  
pp. 1409-1426 ◽  
Author(s):  
Núria Nieto-Nicolau ◽  
Beatriz Martín-Antonio ◽  
Claudia Müller-Sánchez ◽  
Ricardo P Casaroli-Marano

Aim: To determine the potential of mesenchymal stem cells (MSC) for corneal epithelial regeneration in vitro. Materials & methods: Bone marrow MSC (BM-MSC) and adipose tissue MSC were analyzed for corneal epithelial and mesenchymal markers, using limbal stem cells and corneal cells as controls. MSC with better potential were cultured with specific mediums for epithelial induction. Transepithelial electric resistance and wound healing assay with human corneal epithelial cells were performed. Results: BM-MSC showed better potential, increased corneal markers, and higher transepithelial electric resistance values when induced with limbal epithelial culture medium. Induced BM-MSC promoted better wound healing of human corneal epithelial cells by paracrine secretion. Conclusion: BM-MSC has potential for corneal epithelial induction in a protocol compatible with human application.


2015 ◽  
Vol 56 (2) ◽  
pp. 983-992 ◽  
Author(s):  
M. A. Bermudez ◽  
J. Sendon-Lago ◽  
N. Eiro ◽  
M. Trevino ◽  
F. Gonzalez ◽  
...  

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