The Effect of SPARC on the Proliferation and Migration of Limbal Epithelial Stem Cells during the Corneal Epithelial Wound Healing

2021 ◽  
Author(s):  
Le-yi Wang ◽  
Yu-ting Zhang ◽  
Li-qun Du ◽  
Xinyi Wu ◽  
Jing Zhu
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Epithelial Stem Cells ◽  
Corneal Epithelial ◽  
Epithelial Wound Healing ◽  
Limbal Epithelial Stem Cells ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals Stem Cells in the Path of Light, from Corneal to Retinal Reconstruction

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 873
Author(s):  
Ovidiu Samoila ◽  
Lacramioara Samoila
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Clinical Success ◽  
Corneal Stroma ◽  
Cell Transplant ◽  
Inclusion Criteria ◽  
Epithelial Stem Cells ◽  
Corneal Epithelial ◽  
Stem Cells Transplantation ◽  
Limbal Epithelial Stem Cells

The future of eye reconstruction invariably includes stem cells transplantation. Corneal limbus, corneal stroma, trabeculum, retinal cells, optic nerve, and all structures that are irreversibly damaged and have no means to be repaired or replaced, through conventional treatment or surgery, represent targets for stem cell reconstruction. This review tries to answer the question if there is any clinical validation for stem therapies, so far, starting from the cornea and, on the path of light, arriving to the retina. The investigation covers the last 10 years of publications. From 2385 published sources, we found 56 clinical studies matching inclusion criteria, 39 involving cornea, and 17 involving retina. So far, corneal epithelial reconstruction seems well validated clinically. Enough clinical data are collected to allow some form of standardization for the stem cell transplant procedures. Cultivated limbal epithelial stem cells (CLET), simple limbal epithelial transplant (SLET), and oral mucosa transplantation are implemented worldwide. In comparison, far less patients are investigated in retinal stem reconstructions, with lower anatomical and clinical success, so far. Intravitreal, subretinal, and suprachoroidal approach for retinal stem therapies face specific challenges.

Corneal Epithelial Wound Healing and Bactericidal Effect of Conditioned Medium From Human Uterine Cervical Stem Cells

2015 ◽  
Vol 56 (2) ◽  
pp. 983-992 ◽  
Author(s):  
M. A. Bermudez ◽  
J. Sendon-Lago ◽  
N. Eiro ◽  
M. Trevino ◽  
F. Gonzalez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Conditioned Medium ◽  
Bactericidal Effect ◽  
Corneal Epithelial ◽  
Epithelial Wound Healing

scholarly journals YAP, ΔNp63, and β-Catenin Signaling Pathways Are Involved in the Modulation of Corneal Epithelial Stem Cell Phenotype Induced by Substrate Stiffness

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 347 ◽  
Author(s):  
Ricardo M. Gouveia ◽  
Flora Vajda ◽  
Jason A. Wibowo ◽  
Francisco Figueiredo ◽  
Che J. Connon
Keyword(s):  
Stem Cells ◽  
Signaling Pathways ◽  
Biomechanical Properties ◽  
Substrate Stiffness ◽  
Future Research ◽  
Cell Phenotype ◽  
Epithelial Stem Cells ◽  
Corneal Epithelial ◽  
Proliferative Markers ◽  
Limbal Epithelial Stem Cells

Recent studies have established that the phenotype of epithelial stem cells residing in the corneal periphery (the limbus) depends on this niche’s distinct biomechanical properties. However, the signaling pathways underlying this dependency are still poorly understood. To address this issue, we investigated the effect of substrate stiffness on the migration, proliferation, and molecular phenotype of human limbal epithelial stem cells (LESCs). Specifically, we demonstrated that cells grown on collagen-based substrates with limbus-like compliance showed higher proliferation and stratification and lower migration capabilities, as well as higher levels of pro-proliferative markers Ki67 and β-Catenin, and LESC markers ΔNp63, ABCG2, and CK15. In contrast, cells on stiffer substrates lost these stem/progenitor cell markers, but instead expressed the key mechanotransduction factor YAP, as well as elevated levels of BMP4, a promotor of cell differentiation known to be negatively regulated by Wnt/β-Catenin signaling. This data allowed us to propose a new model that integrates the various molecular pathways involved in LESC response to substrate stiffness. This model will potentially be a useful guide to future research on the mechanisms underlying LESC loss following fibrosis-causing injuries.

scholarly journals Peripheral (not central) corneal epithelia contribute to the closure of an annular debridement injury

2019 ◽  
Vol 116 (52) ◽  
pp. 26633-26643 ◽  
Author(s):  
Mijeong Park ◽  
Alexander Richardson ◽  
Elvis Pandzic ◽  
Erwin P. Lobo ◽  
J. Guy Lyons ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Essential Role ◽  
Wound Closure ◽  
Cell Behavior ◽  
Epithelial Stem Cells ◽  
Self Renewal ◽  
Central Cornea ◽  
Limbal Epithelial Stem Cells

Corneal epithelia have limited self-renewal and therefore reparative capacity. They are continuously replaced by transient amplifying cells which spawn from stem cells and migrate from the periphery. Because this view has recently been challenged, our goal was to resolve the conflict by giving mice annular injuries in different locations within the corneolimbal epithelium, then spatiotemporally fate-mapping cell behavior during healing. Under these conditions, elevated proliferation was observed in the periphery but not the center, and wounds predominantly resolved by centripetally migrating limbal epithelia. After wound closure, the central corneal epithelium was completely replaced by K14+limbal-derived clones, an observation supported by high-resolution fluorescence imaging of genetically marked cells in organ-cultured corneas and via computational modeling. These results solidify the essential role of K14+limbal epithelial stem cells for wound healing and refute the notion that stem cells exist within the central cornea and that their progeny have the capacity to migrate centrifugally.

scholarly journals Umbilical Cord Mesenchymal Stem Cells-derived Exosomes Deliver Mir-21 to Accelerate Corneal Epithelial Wound Healing Through PTEN/PI3K/Akt pathway

2021 ◽  
Author(s):  
Xuran Li ◽  
Xiaolong Liu ◽  
Yanyan Zhang ◽  
Zhiyu Liu ◽  
Xinyue Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Wound Repair ◽  
Recipient Cell ◽  
Human Umbilical Cord ◽  
Corneal Epithelial ◽  
Epithelial Wound Healing

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.

scholarly journals Human Adipose-Derived Stem Cells Promote Seawater-Immersed Wound Healing by Activating Skin Stem Cells via the EGFR/MEK/ERK Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Jiachao Xiong ◽  
Boyao Ji ◽  
Liujun Wang ◽  
Yazhou Yan ◽  
Zhixiao Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Skin Wounds ◽  
Adipose Derived Stem Cells ◽  
Delayed Wound Healing ◽  
Cell Proliferation And Migration ◽  
Thickness Skin ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Proliferation And Migration

Seawater (SW) immersion can increase the damage of skin wounds and produce refractory wounds. However, few studies have been conducted to investigate the mechanisms of SW immersion on skin wounds. In our current study, we investigated the effect of human adipose-derived stem cells (hADSCs) on the repair of SW-treated full-thickness skin wounds and the underlying mechanisms. The results showed that SW immersion could reduce the expression of EGF and suppress the activation of the MEK/ERK signaling pathway. At the same time, the proliferation and migration of skin stem cells were inhibited by SW immersion, resulting in delayed wound healing. However, hADSCs significantly accelerated the healing of SW-immersed skin wounds by promoting cell proliferation and migration through the aforementioned mechanisms. Our results indicate a role for hADSCs in the repair of seawater-immersed skin wounds and suggest a potential novel treatment strategy for seawater-immersed wound healing.

scholarly journals Hindlimb unloading depresses corneal epithelial wound healing in mice

2004 ◽  
Vol 97 (2) ◽  
pp. 641-647 ◽  
Author(s):  
Zhijie Li ◽  
Chantal A. Rivera ◽  
Alan R. Burns ◽  
C. Wayne Smith
Keyword(s):  
Wound Healing ◽  
Inflammatory Response ◽  
Wound Repair ◽  
Hindlimb Unloading ◽  
Delayed Wound Healing ◽  
Corneal Epithelial ◽  
Epithelial Migration ◽  
Epithelial Wound Healing ◽  
And Migration ◽  
Neutrophil Response

C57BL/6 mice were subjected to hindlimb unloading (HU) for a period of 3 wk to determine the possible effects on epithelial wound healing. A standardized corneal epithelial wound was performed, and parameters of the inflammatory response and reepithelialization were analyzed over an observation period of 96 h. Wound closure was significantly retarded in mice during HU with reepithelialization being delayed by ∼12 h. Both epithelial migration and cell division were significantly depressed and delayed. The inflammatory response to epithelial wounding was also significantly altered during HU. Neutrophils, as detected by the Gr-1 marker, were initially elevated above normal levels before wounding and during the first few hours afterward, but there was a significant reduction in neutrophil response to wounding at times where neutrophil influx and migration in controls were vigorous. A similar pattern was seen with CD11b+CD11c+ cells (monocyte lineage). Langerhans cells are normally resident within the peripheral corneal epithelium. They respond to injury by initially leaving the epithelial site within 6 h and returning to normal levels by 96 h, 2 days after reepithelialization is complete. During HU, this pattern is distinctly different, with Langerhans cell numbers slowly diminishing, reaching a nadir at 96 h, which is significantly below normal. Evidence for systemic effects of HU is provided by findings that collagen deposition within subcutaneous sponges was significantly reduced during HU. In conclusion, HU, a ground-based model simulating some physiological aspects of spaceflight, impairs wound repair of corneas. Multiple factors, both local and systemic, likely contribute to this delayed wound healing.

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