Mesenchymal stem cell transplantation in a rabbit corneal alkali burn model: engraftment and involvement in wound healing

Ye, J; Yao, Ke; Kim, J C

doi:10.1038/sj.eye.6701913

Cited by 136 publications

(132 citation statements)

References 31 publications

(33 reference statements)

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“…We chose to administer the MSCs before transplantation (day À7) as previous studies have shown enhanced efficacy when applied pretransplantation in preclinical models of cardiac (34) and kidney (35) transplantation. To date, a number of groups have investigated the ability of MSCs to repair chemically damaged corneas (20,(36)(37)(38) but relatively few have reported on the effects of MSCs on corneal allograft survival (22,39). To our knowledge, we show here for the first time that MSCs derived from a thirdparty strain are effective in prolonging corneal allograft survival.…”

Section: Discussionmentioning

confidence: 60%

Mesenchymal Stem Cell Therapy Promotes Corneal Allograft Survival in Rats by Local and Systemic Immunomodulation

Treacy

O’Flynn

Ryan

et al. 2014

American Journal of Transplantation

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y These authors contributed equally to this work.Mesenchymal stem cells (MSCs) are being investigated extensively due to their ability to dampen immune responses. Here, we tested the ability of MSCs from three distinct sources to prolong rat corneal allograft survival. A fully allogeneic rat cornea transplant model (DA to LEW) was used. Recipient rats received 1 Â 10 6 MSCs (syn [LEW], allo [DA] or third-party [Wistar Furth]) intravenously 7 days before transplantation and again on the day of transplantation (day 0). A high percentage of untreated and syn-MSC treated allografts were rejected (80% and 100%, respectively). Preactivation of syn-MSCs with interferon gamma also failed to prolong allograft survival. Conversely, corneal allograft survival was significantly prolonged in allo-MSC treated (90%) and third-party MSC treated (80%) allograft recipients. Flow cytometric analysis revealed less infiltrating natural killer T cells in corneas of both allo-and third-party MSC treated animals, coupled with a higher proportion of splenic CD4þFoxp3þ regulatory T cells, compared to controls. In the case of allo-and third-party MSCs, results from a delayed-type hypersensitivity assay clearly showed that hypo-responsiveness was specific for corneal donor-associated alloantigens. Thus, allo-and third-party MSC treatment prolongs corneal allograft survival by suppressing peripheral immune responses and promoting an intragraft immunoregulatory milieu.

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Section: Discussionmentioning

confidence: 60%

Mesenchymal Stem Cell Therapy Promotes Corneal Allograft Survival in Rats by Local and Systemic Immunomodulation

Treacy

O’Flynn

Ryan

et al. 2014

American Journal of Transplantation

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“…Bone marrow derived cells formed approximately half of the pericytes but none of the endothelial cells of the new vessels in a mouse model of experimental corneal neovascularization (147). Recently, bone marrow derived progenitor cells were shown to promote wound healing and re-epithelization in alkali injured rabbit corneas (148,149).…”

Section: Stromal Stem Cellsmentioning

confidence: 99%

Stem cells of the adult cornea: From cytometric markers to therapeutic applications

et al. 2008

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The cornea is a major protective shield of the interior of the eye and represents two thirds of its refractive power. It is made up of three tissue layers that have different developmental origins: the outer, epithelial layer develops from the ectoderm overlying the lens vesicle, whereas the stroma and the endothelium have mesenchymal origin. In the adult organism, the outermost corneal epithelium is the most exposed to environmental damage, and its constant renewal is assured by the epithelial stem cells that reside in the limbus, the circular border of the cornea. Cell turnover in the stromal layer is very slow and the endothelial cells probably do not reproduce in the adult organism. However, recent experimental evidence indicates that stem cells may be found in these layers. Damage to any of the corneal layers leads to loss of transparency and low vision. Corneal limbal stem cell deficiency results in severe ocular surface disease and its treatment by transplantating ex vivo expanded limbal epithelial cells is becoming widely accepted today. Stromal and endothelial stem cells are potential tools of tissue engineering and regenerative therapies of corneal ulcers and endothelial cell loss. In the past few years, intensive research has focused on corneal stem cells aiming to improve the outcomes of the current corneal stem cell transplantation techniques. This review summarizes the current state of knowledge on corneal epithelial, stromal and endothelial stem cells. Special emphasis is placed on the molecular markers that may help to identify these cells, and the recently revealed mechanisms that could maintain their ''stemness'' or drive their differentiation. The techniques for isolating and culturing/ expanding these cells are also described. '

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“…These findings are in agreement with the observation of Lan et al [28], who detected systemically administered MSCs on day 3 in the cauterized cornea but not in the contralateral cornea. Systemically administered MSCs were also detected in the cornea 14 days after their injection in a rabbit eye alkali-burn model [29] but not in the case of xenogeneic (human) MSCs administered systemically in order to heal a corneal injury in the rat [19].…”

Section: Discussionmentioning

confidence: 98%

Modulation of the Early Inflammatory Microenvironment in the Alkali-Burned Eye by Systemically Administered Interferon-γ-Treated Mesenchymal Stromal Cells

Javorková

Trošan

Zajı́cová

et al. 2014

Stem Cells and Development

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The aim of this study was to investigate the effects of systemically administered bone-marrow-derived mesenchymal stromal cells (MSCs) on the early acute phase of inflammation in the alkali-burned eye. Mice with damaged eyes were either untreated or treated 24 h after the injury with an intravenous administration of fluorescent-dye-labeled MSCs that were unstimulated or pretreated with interleukin-1a (IL-1a), transforming growth factor-b (TGF-b), or interferon-g (IFN-g). Analysis of cell suspensions prepared from the eyes of treated mice on day 3 after the alkali burn revealed that MSCs specifically migrated to the damaged eye and that the number of labeled MSCs was more than 30-times higher in damaged eyes compared with control eyes. The study of the composition of the leukocyte populations within the damaged eyes showed that all types of tested MSCs slightly decreased the number of infiltrating lymphoid and myeloid cells, but only MSCs pretreated with IFN-g significantly decreased the percentage of eye-infiltrating cells with a more profound effect on myeloid cells. Determining cytokine and NO production in the damaged eyes confirmed that the most effective immunomodulation was achieved with MSCs pretreated with IFN-g, which significantly decreased the levels of the proinflammatory molecules IL-1a, IL-6, and NO. Taken together, the results show that systemically administered MSCs specifically migrate to the damaged eye and that IFN-g-pretreated MSCs are superior in inhibiting the acute phase of inflammation, decreasing leukocyte infiltration, and attenuating the early inflammatory environment.

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Mesenchymal stem cell transplantation in a rabbit corneal alkali burn model: engraftment and involvement in wound healing

Cited by 136 publications

References 31 publications

Mesenchymal Stem Cell Therapy Promotes Corneal Allograft Survival in Rats by Local and Systemic Immunomodulation

Mesenchymal Stem Cell Therapy Promotes Corneal Allograft Survival in Rats by Local and Systemic Immunomodulation

Stem cells of the adult cornea: From cytometric markers to therapeutic applications

Modulation of the Early Inflammatory Microenvironment in the Alkali-Burned Eye by Systemically Administered Interferon-γ-Treated Mesenchymal Stromal Cells

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