Mesenchymal Stem Cell-Based Therapy for Retinal Degenerative Diseases: Experimental Models and Clinical Trials

Abstract

Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy or glaucoma, represent the main causes of a decreased quality of vision or even blindness worldwide. However, despite considerable efforts, the treatment possibilities for these disorders remain very limited. A perspective is offered by cell therapy using mesenchymal stem cells (MSCs). These cells can be obtained from the bone marrow or adipose tissue of a particular patient, expanded in vitro and used as the autologous cells. MSCs possess potent immunoregulatory properties and can inhibit a harmful inflammatory reaction in the diseased retina. By the production of numerous growth and neurotrophic factors, they support the survival and growth of retinal cells. In addition, MSCs can protect retinal cells by antiapoptotic properties and could contribute to the regeneration of the diseased retina by their ability to differentiate into various cell types, including the cells of the retina. All of these properties indicate the potential of MSCs for the therapy of diseased retinas. This view is supported by the recent results of numerous experimental studies in different preclinical models. Here we provide an overview of the therapeutic properties of MSCs, and their use in experimental models of retinal diseases and in clinical trials.

The Role of Inflammation in Retinal Neurodegeneration and Degenerative Diseases

“…The impairment of the integrity of the retina slowly progresses and finally disintegrates the lining of the retinal cells or causes the death of the specialized light-sensing retinal cells known as photoreceptors that provide visual input to the brain [ 13 ]. This cycle worsens over time, resulting in visual deterioration and subsequently blindness or complete vision loss [ 14 ].…”

Cell-Based Neuroprotection of Retinal Ganglion Cells in Animal Models of Optic Neuropathies

“…MSCs comprise a population of multipotent adult stem cells that can be relatively easily isolated from different tissues with low invasiveness and subsequently expanded in vitro, permitting their use in autologous transplantation settings and thus avoiding rejection problems associated with most other stem cell types [ 57 , 58 ]. Due to their anti-apoptotic and immunomodulatory activities, MSCs are considered as promising candidate cells for the development of therapies for the treatment of neurodegenerative diseases [ 45 , 46 , 59 , 60 ]. MSCs can be derived, for instance, from bone marrow (bone marrow-derived MSCs (BMSCs)), adipose tissue (adipose-derived MSCs, (ADSCs)), dental tissues, such as dental pulp (dental pulp stem cells, (DPSCs)), umbilical cord blood (umbilical cord blood-derived MSCs (UCB-MSCs)) or umbilical cord Wharton’s jelly (umbilical cord Wharton’s jelly-derived MSCs (WJ-MSCs)) [ 45 , 51 , 58 ].…”

“…The therapeutic potential of MSCs for the treatment of optic neuropathies is being evaluated in several clinical trials ( (accessed on 14 October 2021)), but information about the outcomes is limited [reviewed in: [ 25 , 46 , 54 , 181 , 182 ]].…”

“…This aim might be achieved through a viral or nonviral gene transfer to the dystrophic retinas or through intraocular implantations of NTF-loaded slow-release devices [ 14 , 25 , 41 , 42 , 43 , 44 ]. Intraocular transplantations of diverse genetically non-modified cell types have also been shown to confer significant protection to RGCs under a variety of pathological conditions through secretion of immunomodulatory mediators, NTFs and exosomes [ 34 , 45 , 46 , 47 , 48 , 49 , 50 ].…”

The Vertical and Horizontal Pathways in the Monkey Retina Are Modulated by Typical and Atypical Cannabinoid Receptors

“…), there are little approved clinical treatments for retinal diseases like age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, and retinitis pigmentosa (RP). However, intense research is being carried out targeting these pathologies using a wide variety of approaches [58][59][60][61][62][63]. Current strategies focus on slowing down or stop the initial triggers (e.g., AREDS supplementation, exercise, eating well, and smoking cessation in dry AMD, and anti-VEGF intraocular injections in wet AMD) [64,65], or focus on relieving the symptoms (e.g., lowering intraocular pressure (IOP) with prostaglandin analogues or beta blockers in glaucoma) [66].…”