The Anti-Inflammatory and Anti-Angiogenic Role of Mesenchymal Stem Cells in Corneal Wound Healing Following Chemical Injury

Oh, Joo Youn; Kim, Mee Kum; Shin, Mi Sun; Lee, Hyun Ju; Ko, Jung Hwa; Wee, Won Ryang; Lee, Jin Hak

doi:10.1634/stemcells.2007-0737

Cited by 353 publications

(300 citation statements)

References 38 publications

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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: 70%

“…Considering the regenerative potential and profound immunosuppressive effects of MSCs, MSC therapy is a promising approach for the treatment of inflammatory diseases and prevention of graft rejection (for review see [19]). Recently, treatment of experimental corneal injuries in rabbits and limbal stem cell deficiencies in rats with MSCs has been reported (20,21); however, very little is known about the role of MSCs in the prevention of corneal allograft rejection. One recent study did report the therapeutic benefit of human MSC infusion in a fully allogeneic mouse model of cornea transplantation (22).…”

Section: Introductionmentioning

confidence: 99%

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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: 70%

Section: Introductionmentioning

confidence: 99%

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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“…Further, VEGF overexpressing bone marrow stem cells demonstrate greater protection of injured tissue than controls. Thus, VEGF, HGF, and FGF2 may be important paracrine signaling molecules in stem cell-mediated angiogenesis, protection, and survival (26)(27)(28)(29)(30) . …”

Section: B1) Increased Angiogenesismentioning

confidence: 99%

Possible mechanisms of retinal function recovery with the use of cell therapy with bone marrow-derived stem cells

Siqueira¹,

Voltarelli²,

Messias³

et al. 2010

Arq. Bras. Oftalmol.

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“…12 It improves the corneal reepithelialization and reduces the anti-inflammatory acute phase through the release of soluble factors. 13 It is constituted of a single layer of epithelial cells that lie on the basement membrane, which is adjacent to a compact layer of collagen. AM is easily isolated from the placenta after a cesarean delivery and can be cryopreserved for several months.…”

mentioning

confidence: 99%

In VitroCharacterization of Patches of Human Mesenchymal Stromal Cells

Roux

Bodivit

Bartis

et al. 2015

Tissue Engineering Part A

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Stem cells may represent an excellent strategy to improve the healing of skin ulcers. Today the administration mode of stem cells to skin defects remains unsatisfactory. Delivering stem cells with topical treatments represents a new strategy and answering the patients' need. Mesenchymal stromal cells (MSC) have been shown to improve wound healing of cutaneous lesions and amniotic membrane (AM) is known to represent a natural scaffold for cells. The aim of this study is to develop a tissue-engineered product combining MSC and AM for clinical use. In this work we investigated whether the stromal matrix of intact human AM could constitute a scaffold for human MSC derived from either bone marrow (BM) or adipose tissue (AT). For this purpose, clinical-grade AM, MSC, and culture medium were used. We performed experiments of short-term adherence and proliferation for 15 days after the seeding of the cells. Morphological aspects and secretion profiles of MSC onto AM were studied, respectively, by scanning electron microscopy and Luminex analysis. Results demonstrated that the stromal matrix allow the adherence in much greater amount of MSC from BM or AT compared to 2D material. Experiments of proliferation showed that both kinds of MSC could proliferate on the stromal matrix and remain viable 15 days after the seeding of the cells. The 3D analysis of MSC culture demonstrated that both types of MSC invaded the stromal matrix and grew in multiple layers while retaining their fibroblastic morphology. By studying the secretion profile of MSC onto the stromal matrix, we found that both kinds of MSC secrete important cytokines and growth factors for wound healing of cutaneous lesions, such as vascular endothelial growth factor, hepatocyte growth factor, and basic fibroblast growth factor. In conclusion, these results suggest that the stromal matrix of AM seeded with MSC represents a bioactive scaffold that should be evaluated in patients with a nonhealing cutaneous wound.

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The Anti-Inflammatory and Anti-Angiogenic Role of Mesenchymal Stem Cells in Corneal Wound Healing Following Chemical Injury

Cited by 353 publications

References 38 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

Possible mechanisms of retinal function recovery with the use of cell therapy with bone marrow-derived stem cells

In VitroCharacterization of Patches of Human Mesenchymal Stromal Cells

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