Therapeutic Potential of Mesenchymal Stem Cells in the Treatment of Ocular Graft-Versus-Host Disease

Abstract

Ocular GVHD (oGVHD), manifested by severe injury of corneal epithelial cells, meibomian and lacrimal glands’ dysfunction, is a serious complication of systemic GVHD which develops as a consequence of donor T and natural killer cell-driven inflammation in the eyes of patients who received allogeneic hematopoietic stem cell transplantation. Mesenchymal stem cells (MSC) are, due to their enormous differentiation potential and immunosuppressive characteristics, considered as a potentially new remedy in ophthalmology. MSC differentiate in corneal epithelial cells, suppress eye inflammation, and restore meibomian and lacrimal glands’ function in oGVHD patients. MSC-sourced exosomes (MSC-Exos) are extracellular vesicles that contain MSC-derived growth factors and immunoregulatory proteins. Due to the lipid membrane and nano-sized dimension, MSC-Exos easily by-pass all biological barriers in the eyes and deliver their cargo directly in injured corneal epithelial cells and eye-infiltrated leukocytes, modulating their viability and function. As cell-free agents, MSC-Exos address all safety issues related to the transplantation of their parental cells, including the risk of unwanted differentiation and aggravation of intraocular inflammation. In this review article, we summarized current knowledge about molecular mechanisms which are responsible for beneficial effects of MSC and MSC-Exos in the therapy of inflammatory eye diseases, emphasizing their therapeutic potential in the treatment of oGVHD.

Targeting the Ophthalmic Diseases Using Extracellular Vesicles ‘Exosomes’: Current Insights on Their Clinical Approval and Present Trials

“…Modulation of the IL-6/IL-6R/Stat3 pathway by miRNA-204 played a crucial role in attenuating this disease [101]. The therapeutic potential of MSC-derived exosomes in cGvHD-induced dry eye disease was further validated by Harrell et al [102].…”

Cellular microenvironment: a key for tuning mesenchymal stem cell senescence

“…( Zhuang et al, 2022 ). To date, treatments using MSCs and their extracellular vesicles (EVs) have demonstrated beneficial effects in a variety of diseases, such as osteoarthritis (OA) ( Greif et al, 2020 ; Kim et al, 2020 ; Rizzo et al, 2023 ), diabetic mellitus (DM) ( Sun F. et al, 2022 ; Yang et al, 2022 ), Crohn’s disease (CD) ( Garcia-Olmo et al, 2022 ; Huang et al, 2022 ), systemic lupus erythematosus (SLE) ( Zhang Mingchao et al, 2022 ), myocardial infarction (MI) ( Czosseck et al, 2022 ), acute respiratory distress disorder (ARD) ( Jackson et al, 2016 ; Qiao et al, 2021 ) and graft-versus-host disease (GVHD) ( Harrell et al, 2022 ). In 2006, the International Society for Cellular Therapy (ISCT) proposed minimal criteria to define MSCs.…”