Potential of mesenchymal stem cells as topical immunomodulatory cell therapies for ocular surface inflammatory disorders

Abstract

Ocular surface inflammatory disorders (OSIDs) are a group of highly prevalent, heterogeneous diseases which display a variety of aetiologies and symptoms and are risk factors for serious complications including ocular and cornea impairment. Corneal inflammation is a common factor of all OSIDs, regardless of their cause or symptoms. Current medications include over-the-counter lubricating eye drops, corticosteroids, and ciclosporin, which either do not treat the corneal inflammation or have been associated with multiple side effects leading to alternative treatments being sought. Regenerative medicine cell therapies, particularly mesenchymal stem cells (MSCs), have shown great promise for immunosuppression and disease amelioration across multiple tissues, including the cornea. However, for successful development and clinical translation of MSC therapy for OSIDs, significant problems must be addressed. This review aims to highlight considerations, including whether the source of MSC isolation impacts the efficacy and safety of the therapy, in addition to assessing the feasibility of MSC topical application to the cornea and ocular surface through analysis of potential scaffolds and cell carriers for application to the eye. The literature contains limited data assessing MSCs incorporated into scaffolds for corneal administration, thus here we highlight the necessity of further investigations to truly exploit the potential of an MSC-based cell therapy for the treatment of OSIDs.

Translational and Regulatory Challenges of Corneal Endothelial Cell Therapy: A Global Perspective

“…Although HCEnC therapy was used as a point of reference for discussion, many of the underpinning principles and challenges are applicable to the broader development of other cell therapies such as those derived from hematopoietic cells, MSCs, lymphocytes, and dendritic cells, among others. 95,96 While harmonizing the regulatory framework across different regions would be challenging, a clear overview on the similarity and disparity of different regional frameworks would facilitate the navigation and development of CTPs from bench to bedside for the academics, industrial partners, and relevant stakeholders.…”

The Effect of Limbal Mesenchymal Stem Cell Secretome on Corneal Neovascularization in Experimental Model of Corneal Alkali Injury

“…Corneal neovascularization can occur when there is an imbalance between proangiogenic and antiangiogenic factors which there are excessive pro-angiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase (MMP), while there is a deficiency of anti-angiogenic factors such as pigment epithelium-derived factor, angiostatin, endostatin and thrombospondin. MSC inhibit corneal neovascularization by downregulating pro-angiogenic factors (VEGF, MMP) and upregulating anti-angiogenic factors (TSP-1, PEDF, sLFT-1, TSG-6) (Beeken et al, 2020;Eslani et al, 2017;Oh et al, 2008;Ghazaryan et al, 2016;Komaratih et al, 2019;Song et al, 2018;Yao et al, 2012).…”

“…Mesenchymal stem cell secretome has been investigated to have the role as an antiinflammatory, anti-angiogenesis, and immunomodulatory. Several studies have shown that MSC not only reduces inflammation and reduces corneal opacity, but can also significantly inhibits neovascularization in corneal chemical injury (Almaliotis et al, 2015;Cejka et al, 2016;Beeken et al, 2020;Ke et al, 2015;Ma et al, 2006;Pawitan, 2014). The aim of this study is to analyze the effect of limbal mesenchymal stem cell (L-MSC) secretome in inhibition of corneal neovascularization in an animal model of alkali chemical injury by evaluating corneal neovascularization clinically and histopathologically.…”

Small extracellular vesicles from menstrual blood-derived mesenchymal stem cells (MenSCs) as a novel therapeutic impetus in regenerative medicine

“…They possess powerful self-renewal ability and multilineage differentiation potential via symmetric/asymmetric cell division [3][4][5]. Currently, MSC-based therapy has been diffusely exploited in the treatment of numerous diseases in basic science and clinical medicine [6][7][8][9][10][11][12].…”