A Comparative Study of the Therapeutic Potential of Mesenchymal Stem Cells and Limbal Epithelial Stem Cells for Ocular Surface Reconstruction

Abstract

Corneal regeneration x Stem cell-based therapy ABSTRACTStem cell-based therapy has become an attractive and promising approach for the treatment of severe injuries or thus-far incurable diseases. However, the use of stem cells is often limited by a shortage of available tissue-specific stem cells; therefore, other sources of stem cells are being investigated and tested. In this respect, mesenchymal stromal/stem cells (MSCs) have proven to be a promising stem cell type. In the present study, we prepared MSCs from bone marrow (BM-MSCs) or adipose tissue (Ad-MSCs) as well as limbal epithelial stem cells (LSCs), and their growth, differentiation, and secretory properties were compared. The cells were grown on nanofiber scaffolds and transferred onto the alkaliinjured eye in a rabbit model, and their therapeutic potential was characterized. We found that BM-MSCs and tissue-specific LSCs had similar therapeutic effects. Clinical characterization of the healing process, as well as the evaluation of corneal thickness, re-epithelialization, neovascularization, and the suppression of a local inflammatory reaction, were comparable in the BM-MSC-and LSC-treated eyes, but results were significantly better than in injured, untreated eyes or in eyes treated with a nanofiber scaffold alone or with a nanofiber scaffold seeded with Ad-MSCs. Taken together, the results show that BM-MSCs' therapeutic effect on healing of injured corneal surface is comparable to that of tissuespecific LSCs. We suggest that BM-MSCs can be used for ocular surface regeneration in cases when autologous LSCs are absent or difficult to obtain. STEM CELLS

Therapeutic Effect of Human Adipose Tissue-Derived Mesenchymal Stem Cells in Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage

“…Our research group and others have demonstrated that AT‐MSCs express corneal epithelial markers under basic culture conditions, suggesting that these cells may have some inherent properties to regenerate the corneal epithelium . In experimental models of LSCD, administration of AT‐MSCs subconjunctivally , topically , or overlaid on scleral contact lenses or nanofiber scaffolds promotes regeneration of the corneal epithelium. Additionally, a case report in which AT‐MSCs were applied topically to a patient with persistent sterile epithelial defects supports the potential benefit of this modality .…”

Concise Review: Stem Cells for Corneal Wound Healing

“…For these reasons, alternative cell sources able to differentiate into the corneal epithelium have been tested for restoration of the corneal surface and wound healing. These include cultured oral mucosal epithelium, hair follicle, conjunctival and epidermal epithelium, amniotic epithelial cells, umbilical cord lining epithelial cells, as well as mesenchymal stem cells (MSCs) from adipose tissue, bone marrow, orbital fat, and immature dental pulp . Cultured autologous oral mucosal epithelium has been used clinically; again, most frequently, for chemical burns, although with somewhat lower success rates than with LESC transplantation (close to 70%) .…”

“…Cultured autologous oral mucosal epithelium has been used clinically; again, most frequently, for chemical burns, although with somewhat lower success rates than with LESC transplantation (close to 70%) . Most other cell types have only been examined in preclinical models .…”

Extrinsic and Intrinsic Mechanisms by Which Mesenchymal Stem Cells Suppress the Immune System

“…97 BMSCs and limbal epithelial stem cells are similarly efficacious for treating limbal cell deficiency after alkali burn. 98 The ability of BMSCs to treat LSCD is attributed not only to transdifferentiation, but also to suppression of local inflammation and secretion of growth factors, thereby supporting the growth of residual corneal epithelial cells. 98 The use of MSCs for treating corneal diseases has recently been reviewed by our group, and the discussion below focuses primarily on the use of MSCs for treating inflammatory response in the ocular surface (Figure 4).…”