Subconjunctival injection of mesenchymal stromal cells protects the cornea in an experimental model of GVHD

Martínez-Carrasco, Rafael; Sánchez‐Abarca, Luis Ignacio; Nieto-Gómez, Cristina; García, Elisabet M. Rascón; Sánchez‐Guijo, Fermín; Argüeso, Pablo; Aijón, José; Hernández-Galilea, Emiliano; Velasco, Almudena

doi:10.1016/j.jtos.2019.01.001

Cited by 42 publications

(31 citation statements)

References 52 publications

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“…Prior subconjunctival injection for LSCD involved mesenchymal stem cells. 44–46 In this study, the injected cells were epithelial-derived and morphologically more similar to corneal epithelial cells. These characteristics enabled them to exist stably in the cornea and help support the recovering of corneal epithelium.…”

Section: Discussionmentioning

confidence: 76%

Subconjunctival Injection of Transdifferentiated Oral Mucosal Epithelial Cells for Limbal Stem Cell Deficiency in Rats

Xiao

Xie

Liu

et al. 2020

J Histochem Cytochem.

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Rat limbal niche cells (LNCs) have been proven to induce transdifferentiation of oral mucosal epithelial cells (OMECs) into corneal epithelial-like cells termed transdifferentiated oral mucosal epithelial cells (T-OMECs). This investigation aimed to evaluate the effect of subconjunctival T-OMEC injections on alkali-induced limbal stem cell deficiency (LSCD) in rats. LNCs were cocultured with OMECs in the Transwell system to obtain T-OMECs, with NIH-3T3 cells serving as a control. Subconjunctival injection of single T-OMEC or OMEC suspension was performed immediately after corneal alkali injury. T-OMECs were prelabeled with the fluorescent dye CM-DiI in vitro and tracked in vivo. Corneal epithelial defect, opacity, and neovascularization were quantitatively analyzed. The degree of corneal epithelial defect (from day 1 onward), opacity (from day 5 onward), and neovascularization (from day 2 onward) was significantly less in the T-OMEC group than in the OMEC group. Cytokeratin 12 (CK12), pigment epithelium–derived factor, and soluble fms-like tyrosine kinase-1 were expressed at a higher rate following T-OMEC injection. Some CM-DiI-labeled cells were found to be coexpressed with CK12, Pax6, and ΔNp63α in the corneal epithelium after subconjunctival injection. Subconjunctival injection of T-OMECs prevents conjunctival invasion and maintains a normal corneal phenotype, which might be a novel strategy in the treatment of LSCD:

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Section: Discussionmentioning

confidence: 76%

Subconjunctival Injection of Transdifferentiated Oral Mucosal Epithelial Cells for Limbal Stem Cell Deficiency in Rats

Xiao

Xie

Liu

et al. 2020

J Histochem Cytochem.

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“…This apparent difference may be explained by the different methodologies used to measure tear osmolarity. Although the use of the TearLab osmometer to measure tear osmolarity in mice has been reported in several studies, 15,58,59 the mean baseline values are generally higher compared with typical readings from healthy human tear samples. 60 It is unclear whether this discrepancy is due to true differences in homeostatic tear osmolarity in mice compared with humans, or due to technical limitations in using this device to reliably measure tear osmolarity in small animals.…”

Section: Discussionmentioning

confidence: 96%

The Effects of Aging on Corneal and Ocular Surface Homeostasis in Mice

Silva

Hill

Downie

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Aging is a risk factor for dry eye disease. The aim of this study was to investigate if aging is associated with a range of signs of dry eye disease, including tear hyperosmolarity, reduced nerve density, and increased dendritic cell number, in mice. METHOD. Healthy C57BL/6 female mice, aged 2 months (young, n ¼ 10) and 22 months (aged, n ¼ 11) were used. Clinical assessments included corneal sensitivity (Cochet-Bonnet esthesiometry), tear secretion (Phenol red thread test), tear film osmolarity (TearLab osmometer), and corneal thickness (optical coherence tomography). The sum length of the corneal superficial terminals and sub-basal nerves, density of vertical nerve projections, and density and tree area of resident epithelial dendritic cells, were assessed using immunofluorescence and confocal microscopy. RESULTS. Aged mice had significantly higher tear secretion, lower corneal sensitivity, and a thicker corneal stroma but thinner epithelium. There was no significant intergroup difference for tear osmolarity. Aged mice showed a significantly lower sum length of nerves in the superficial terminals and sub-basal plexus, relative to young mice. Dendritic cell density and morphology were similar in both groups. CONCLUSIONS. In mice, aging is associated with higher tear secretion and corneal epithelial thinning, together with lower corneal nerve density and sensitivity. However, aging was not significantly associated with changes to tear osmolarity or dendritic cell density or size, despite a significant reduction in total nerve length. These findings demonstrate that aged mice exhibit some changes to ocular surface parameters that parallel the anomalies evident in dry eye disease.

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“…Compared to the control group in sharp contrast, patients with the infusion of MSCs did not show remission during a large multicenter refractory GVHD phase III clinical trial in the United States [91]. Furthermore, the treatment with human-MSCs (hMSCs) by subconjunctival injection is effective in reducing corneal inflammation and squamous metaplasia in ocular GVHD (oGVHD), which makes local treatment with hMSCs a promising strategy for oGVHD [92]. However, a slice of studies held the view that instead of inducing immune tolerance in aGVHD, the treatment of MSCs was involved in breaking the vicious circle of GVH reaction due to the poor long term survival [93].…”

Section: Application In Acute Graft-versus-host Disease (Agvhd)mentioning

confidence: 99%

Mesenchymal stem cells: a promising way in therapies of graft-versus-host disease

et al. 2020

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It is well acknowledged that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for numerous malignant blood diseases, which has also been applied to autoimmune diseases for more than a decade. Whereas graft-versus-host disease (GVHD) occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) as a common serious complication, seriously affecting the efficacy of transplantation. Mesenchymal stem cells (MSCs) derived from a wealth of sources can easily isolate and expand with low immunogenicity. MSCs also have paracrine and immune regulatory functions, leading to a broad application prospect in treatment and tissue engineering. This review focuses on immunoregulatory function of MSCs, factors affecting mesenchymal stem cells to exert immunosuppressive effects, clinical application of MSCs in GVHD and researches on MSC-derived extracellular vesicles (EVs). The latest research progress on MSC in related fields is reviewed as well. The relevant literature from PubMed databases is reviewed in this article.

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Subconjunctival injection of mesenchymal stromal cells protects the cornea in an experimental model of GVHD

Cited by 42 publications

References 52 publications

Subconjunctival Injection of Transdifferentiated Oral Mucosal Epithelial Cells for Limbal Stem Cell Deficiency in Rats

Subconjunctival Injection of Transdifferentiated Oral Mucosal Epithelial Cells for Limbal Stem Cell Deficiency in Rats

The Effects of Aging on Corneal and Ocular Surface Homeostasis in Mice

Mesenchymal stem cells: a promising way in therapies of graft-versus-host disease

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