Empowering Mesenchymal Stem Cells for Ocular Degenerative Disorders

Abstract

Multipotent mesenchymal stem cells (MSCs) have been employed in numerous pre-clinical and clinical settings for various diseases. MSCs have been used in treating degenerative disorders pertaining to the eye, for example, age-related macular degeneration, glaucoma, retinitis pigmentosa, diabetic retinopathy, and optic neuritis. Despite the known therapeutic role and mechanisms of MSCs, low cell precision towards the targeted area and cell survivability at tissue needing repair often resulted in a disparity in therapeutic outcomes. In this review, we will discuss the current and feasible strategy options to enhance treatment outcomes with MSC therapy. We will review the application of various types of biomaterials and advances in nanotechnology, which have been employed on MSCs to augment cellular function and differentiation for improving treatment of visual functions. In addition, several modes of gene delivery into MSCs and the types of associated therapeutic genes that are important for modulation of ocular tissue function and repair will be highlighted.

Keywords: degeneration; mesenchymal stem cells; ocular disorders.

Figure 1

Current failures in cell therapy. (A) The patient’s age and mechanical and pathological conditions are among the factors that affect the therapeutic potential of cell therapy. In particular, transplanted cell survival may be affected by (i) mechanical stress during the transplantation procedure; (ii) a harsh microenvironment due to the activation of inflammation-related factors; (iii) oxygen and nutrient starvation due to poorly vascularized environments at the site of implantation; and (iv) a lack of optimization of the delivery protocols. (B) The benefits of cell transplantation could be improved by donor cell preconditioning or modifying transplanted cells prior to implantation to support or enhance their resistance to hypoxic stress. (C) The tissue engineering approach could enhance the survival of transplanted cells through the use of suitable biomaterials as carriers, such as a biologic-derived ECM scaffold. O₂ = oxygen; Bcl-2 = B-cell lymphoma 2; EPO = erythropoietin.

Figure 2

Strategies for empowering mesenchymal stem cells for ocular degenerative disorders. (A) The development of biomaterials can be utilized with or without the addition of growth factors or cytokines that may selectively promote multipotent mesenchymal stem cells (MSCs) either to restore or differentiate into desired cells. (B) Biomaterial can also be 3D-printed to form a sheet or layer of cells that resembles the local environment of the damaged site (Right). (C) MSCs can also be encapsulated or coated with nanoparticles of various sizes or origins to enhance the native property of MSCs. (D) Genetic modification of MSCs can be achieved by introducing MSCs with genes containing beneficial trophic factors or cytokines that could affect the physiological behavior of MSCs.