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![The basic retinal structure. Histological appearance of choroid and retinal layers. The retina is arranged in different layers of cells, from Retinal Pigment Epithelium (RPE), Outer Nuclear Layer (ONL), Outer Plexiform Layer (OPL), Inner Nuclear Layer (INL), Inner Plexiform Layer (IPL), and ganglion cell layer. The retinal layer harbors five retinal neuronal cells, primarily, the rod-and cone-photoreceptors, the Müller glia, the horizontal cell, the bipolar cell, the amacrine cell, and the Retinal Ganglion Cell (RGC). The arrow indicates the light transmission into the retina. Modified with permission from InTech's Publishing Ethics and Legal Affairs Department [5] (© 2012 Triviño A, De Hoz R, Rojas B, Gallego BI, Ramírez AI, Salazar JJ, Ramírez JM. Published in [short citation] under CC BY 3.0 license. Available from: http://dx.doi.org/10.5772/48359).](profile/Pooi-Mok/publication/318758129/figure/fig1/AS:529344739381248@1503217028238/The-basic-retinal-structure-Histological-appearance-of-choroid-and-retinal-layers-The.png)
The basic retinal structure. Histological appearance of choroid and retinal layers. The retina is arranged in different layers of cells, from Retinal Pigment Epithelium (RPE), Outer Nuclear Layer (ONL), Outer Plexiform Layer (OPL), Inner Nuclear Layer (INL), Inner Plexiform Layer (IPL), and ganglion cell layer. The retinal layer harbors five retinal neuronal cells, primarily, the rod-and cone-photoreceptors, the Müller glia, the horizontal cell, the bipolar cell, the amacrine cell, and the Retinal Ganglion Cell (RGC). The arrow indicates the light transmission into the retina. Modified with permission from InTech's Publishing Ethics and Legal Affairs Department [5] (© 2012 Triviño A, De Hoz R, Rojas B, Gallego BI, Ramírez AI, Salazar JJ, Ramírez JM. Published in [short citation] under CC BY 3.0 license. Available from: http://dx.doi.org/10.5772/48359).
Source publication
The use of multipotent mesenchymal stem cells (MSCs) has been reported as promising for the treatment of numerous degenerative disorders including the eye. In retinal degenerative diseases, MSCs exhibit the potential to regenerate into retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Delivery of MSCs was...
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Inflammation underpins and contributes to the pathogenesis of many retinal degenerative diseases. The recruitment and activation of both resident microglia and recruited macrophages, as well as the production of cytokines, are key contributing factors for progressive cell death in these diseases. In particular, the interleukin 1 (IL-1) family consi...
Vision loss causes a significant burden on individuals and communities on a financial, emotional and social level. Common causes include age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and retinitis pigmentosa (RP; also known as 'rod-cone dystrophy'). As the population continues to grow and age globally, an increasing nu...
Retinal degenerative diseases are a group of heterogeneous diseases that include age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR). The progressive degeneration of the retinal neurons results in a severe deterioration of the visual function. Neuroinflammation is an early hallmark of many neurodegenerat...
Traumatic, inherited, and age-related degenerative diseases of the retina, such as retinal detachment, retinitis pigmentosa, and age-related macular degeneration, are characterized by the irreversible loss of retinal neurons. While current treatments aim to prevent neuronal degeneration, there are no available treatments to restore neurons after lo...
Citations
... Any injury in the eye can cause death of these neurons specially photoreceptors and RPE cells leading to irreversible visual defects and blindness. Recent studies therefore targeted the transformation of photoreceptors to make functional RPE layers [40]. Stem cell transplant studies intent to recover visual functions [41]. ...
... IPSCs also showed improvement in the functioning of retina in rats [43]. MSCs could extricate into neurons of retina or could trigger tissue recovery by protecting them from cell death, adjusting inflammation and angiogenesis [40]. ...
Despite the remarkable progress and accomplishments in the fields of medicine and technology, several diseases remain highly fatal or incurable, even in the 21st century. The utilization of stem cells is a viable approach for treating such disorders. The regenerative capacity of stem cells has facilitated the development of treatments for various illnesses that result in organ damage. This review has examined the utility of stem cells in treating a wide range of medical conditions, including vascular disorders, neurological illnesses, autoimmune diseases, ophthalmologic diseases, renal diseases, hepatic diseases, cardiovascular diseases, skeletal diseases, Covid-19, and cancer. It has been determined that stem cells represent the next generation of weapons in the fight against illness and injury.
... Adipose-derived stem cells (ADSCs) are a particular class of mesenchymal stem cell that hold great promise for treating retinal diseases, both acquired and inherited, and have the potential to revolutionize the concept of retinal therapeutics [3]. The purpose of this review is to provide an overview of the therapeutic strategies, modern-day clinical trials, experimental models, and potential clinical use of this class of cells in addressing retinal disorders and diseases and to highlight the current achievements and limitations of this promising technology. ...
With the rapid development of stem cell research in modern times, stem cell-based therapy has opened a new era of tissue regeneration, becoming one of the most promising strategies for currently untreatable retinal diseases. Among the various sources of stem cells, adipose tissue-derived mesenchymal stem cells (ADSCs) have emerged as a promising therapeutic modality due to their characteristics and multiple functions, which include immunoregulation, anti-apoptosis of neurons, cytokine and growth factor secretion, and antioxidative activities. Studies have shown that ADSCs can facilitate the replacement of dying cells, promote tissue remodeling and regeneration, and support the survival and growth of retinal cells. Recent studies in this field have provided numerous experiments using different preclinical models. The aim of our review is to provide an overview of the therapeutic strategies, modern-day clinical trials, experimental models, and potential clinical use of this fascinating class of cells in addressing retinal disorders and diseases.
... By reducing oxidative stress and promoting cell survival, MSCs may contribute to the preservation of retinal function in RP [120]. Finally, it has been demonstrated that MSCs have strong angiogenic potential, as they can promote the formation of new blood vessels by enhancing angiogenesis [115,121]. This is a crucial aspect because, in some cases of RP, vascular abnormalities and compromised blood flow in the retina contribute to disease progression. ...
Retinitis pigmentosa, defined more properly as cone–rod dystrophy, is a paradigm of inherited diffuse retinal dystrophies, one of the rare diseases with the highest prevalence in the worldwide population and one of the main causes of low vision in the pediatric and elderly age groups. Advancements in and the understanding of molecular biology and gene-editing technologies have raised interest in laying the foundation for new therapeutic strategies for rare diseases. As a consequence, new possibilities for clinicians and patients are arising due to the feasibility of treating such a devastating disorder, reducing its complications. The scope of this review focuses on the pathomolecular mechanisms underlying RP better to understand the prospects of its treatment using innovative approaches.
... BMSCs are mainly looked at when studying RP [150]. The ability of BMSCs to fully differentiate into photoreceptors continues to be under investigation, but preclinical studies have demonstrated that BMSCs release anti-angiogenic and neurotrophic factors, as well as immunomodulatory proteins such as insulin-like growth factor-1 (IGF-1), class II major histocompatibility complex (MHC class II) antigens, and Th2-related cytokines [151][152][153]. Brown and colleagues used primitive MSC-derived retinal progenitor cells in rd12 mouse models. ...
Retinitis pigmentosa (RP) is a heterogeneous group of hereditary diseases characterized by progressive degeneration of retinal photoreceptors leading to progressive visual decline. It is the most common type of inherited retinal dystrophy and has a high burden on both patients and society. This condition causes gradual loss of vision, with its typical manifestations including nyctalopia, concentric visual field loss, and ultimately bilateral central vision loss. It is one of the leading causes of visual disability and blindness in people under 60 years old and affects over 1.5 million people worldwide. There is currently no curative treatment for people with RP, and only a small group of patients with confirmed RPE65 mutations are eligible to receive the only gene therapy on the market: voretigene neparvovec. The current therapeutic armamentarium is limited to retinoids, vitamin A supplements, protection from sunlight, visual aids, and medical and surgical interventions to treat ophthalmic comorbidities, which only aim to slow down the progression of the disease. Considering such a limited therapeutic landscape, there is an urgent need for developing new and individualized therapeutic modalities targeting retinal degeneration. Although the heterogeneity of gene mutations involved in RP makes its target treatment development difficult, recent fundamental studies showed promising progress in elucidation of the photoreceptor degeneration mechanism. The discovery of novel molecule therapeutics that can selectively target specific receptors or specific pathways will serve as a solid foundation for advanced drug development. This article is a review of recent progress in novel treatment of RP focusing on preclinical stage fundamental research on molecular targets, which will serve as a starting point for advanced drug development. We will review the alterations in the molecular pathways involved in the development of RP, mainly those regarding endoplasmic reticulum (ER) stress and apoptotic pathways, maintenance of the redox balance, and genomic stability. We will then discuss the therapeutic approaches under development, such as gene and cell therapy, as well as the recent literature identifying novel potential drug targets for RP.
... All of these studies suggest the use of AECs as a replacement anti-fibrotic therapeutic method, like reducing wound inflammation and reprogramming local cells to promote tissue regeneration and fibrosis prevention. The most essential mechanism behind the pharmacological actions of stem cells is thought to be paracrine signaling (Lai et al. 2015;Wu et al. 2017;Litwiniuk and Grzela 2014;Ding et al. 2017). ...
Background
A wound may define as an interruption within the continuity of the epithelial lining of the skin or mucosa that occurs as a result of physical or thermal damage. Wound healing is an intricate process that is highly synchronized censorious in the management of the protective means of the skin. There are a variety of systemic and local factors that influence wound healing, including oxygenation, inflammation, age, stress, diabetes, nutrition, and nicotine. Hemostasis, inflammation, proliferation or granulation, remodeling or maturation are the principle phases of wound healing.
Main body of the abstract
The authors of the current review attempt to convey that the usage of herbal drugs has extreme importance in the current era. The authors reviewed a total of 38 herbal plants with their mechanism of wound healing and the chemical constituents responsible for it. Hyperbaric oxygen therapy, negative pressure therapy, platelet-rich plasma therapy, stem cell therapy, and biosurgery are some of the most often used supporting procedures for wound healing with these herbal drugs.
Short conclusion
There are a variety of herbal plants that have wound healing properties. This evaluation covers a wide range of plants. However, a review of the literature on diverse plants reveals that diverse chemical contents are found in different plant species, but did not mention of which chemical compounds are important for wound healing.
... Second, immunomodulatory properties of MSCs can decrease the pro-inflammatory microenvironment common to retinal degenerative diseases. Third, their secretion of anti-angiogenic factors responsible for inhibiting proangiogenesis is implicated in the etiology of some ocular diseases [19]. As a consequence, this study was conducted to examine histopathological and biochemical effects of VGB on the retina in adult male albino rats and assess the possible therapeutic role of MSCs against this potential toxicity. ...
Vigabatrin (VGB) is an effective antiepileptic drug used mainly to treat infantile spasms and refractory complex partial seizures. However, using VGB was restricted as it was known to cause retinal toxicity that appears as a severe peripheral visual field defect. Accordingly, this study was conducted to examine the histopathological and biochemical effects of VGB on the retina in adult male albino rats and assess the possible therapeutic role of mesenchymal stem cells (MSCs) against this potential toxicity. The rats were divided into three groups (control group, VGB group, and VGB/MSCs group), one week after 65 days of VGB treatment ±MSCs. The right eyeballs were prepared for histological and immunohistochemical examination, whereas the left eyeballs were prepared for real-time polymerase chain reaction analysis. Our results demonstrated that MSCs ameliorated retinal pathological changes and downregulated the expression of glial fibrillary acidic protein, vascular endothelial growth factor, and synaptophysin after VGB administration suggesting MSCs function and vascular modulating effect. Moreover, MSCs regulate retinal tissue gene expression of BAX, Bcl-2, BDNF, NGF, synapsin, interleukin (IL)-6, IL-1β, and occludin suggesting MSCs antiapoptotic and immunomodulating effect. In conclusion, MSCs administration could be a suitable therapeutic line to ameliorate VGB-induced retinopathy.
... MSCs, like stem cells, can differentiate into endodermal and ectodermal lineages thanks to their regenerative potential. Trans-differentiation is defined as a two-step differentiation process that involves the dedifferentiation of terminally differentiated cells and subsequent differentiation into specialized cells of a different lineage [82]. Regarding the ability of MSCs to differentiate into retina-like cells, including RPE cells, there are many extensive data: it has been reported that MSCs can differentiate into cornea-like cells [83,84], neurons [85] or various types of retinal cells [86], including RPE cells, which play an important role in the nourishment of photoreceptors [87]. ...
Inherited retinal dystrophies and retinal degenerations related to more common diseases (i.e., age-related macular dystrophy) are a major issue and one of the main causes of low vision in pediatric and elderly age groups. Advancement and understanding in molecular biology and the possibilities raised by gene-editing techniques opened a new era for clinicians and patients due to feasible possibilities of treating disabling diseases and the reduction in their complications burden. The scope of this review is to focus on the state-of-the-art in somatic cell therapy medicinal products as the basis of new insights and possibilities to use this approach to treat rare eye diseases.
... When transplanted, the nonspecific immunosuppressive therapy and the risk of transplant material rejection are excluded, the minimal susceptibility to malignant tissue degeneration and easy collection of biological material, and compliance with ethical standards are presented [7][8][9][10]. ...
... With the background of prolonged ischemia of the retinal tissue and a decrease in the secretion of growth factors, MSCs can replenish their volume by producing two categories of neurotrophic factors. Some stimulate cell proliferation (transforming growth factor-alpha (TGF-α), TGF-β, hepatocyte growth factor (HGF), epidermal growth factor (EGF) and fibroblast growth factor-4 (FGF-4), others are responsible for maintaining angiogenesis, (VEGF, interleukin-8 (IL-8) and insulin-like growth factor-1 (IGF-1) [10]. The rat models demonstrated the trophic effect of the retinal neuroepithelium by experiment on laser-induced glaucoma and damage to the visual nerve induced. ...
The review provided reveals the analysis of the available scientific literature on the feasibility of using cellular technologies, such as, autologous mesenchymal stem cells (MSCs) for diabetic retinopathy treatment. The results indicated the viability of cellular technologies in clinical ophthalmology with respect to anatomical features and immune privilege of the organ of vision. Additionally, feasibility, safety, and optimization of pathogenetic therapy for MSC transplantation expands the prospect of their use in late complications of type 1 and type 2 diabetes mellitus, in particular, diabetic retinopathy.
... [7] MSCs have the capacity to self-regenerate and can be derived from bone marrow, umbilical cord tissue, dental pulp, and adipose tissue. [1,8] In vitro studies have shown that MSC can differentiate into photoreceptors and RPE within 8-63 days. [7] The therapeutic effect of MSC is observed by the secretion of growth factors upon direct transplantation to the retina and differentiation into retinal tissue or by a paracrine effect. ...
... [7] The therapeutic effect of MSC is observed by the secretion of growth factors upon direct transplantation to the retina and differentiation into retinal tissue or by a paracrine effect. [1,8,9] Furthermore, it also provides anti-apoptotic effects and modulation of immune responses at the inflamed site. [10] The subretinal injection of human-derived umbilical cord mesenchymal stem cells (HDUMSC) in Royal College of Surgeons (RCS) rats with programmed retinal dystrophy showed morphologically improved ONL cell thickness and ERG mixed b-wave responses. ...
Purpose:
This study aimed to investigate the efficacy of human-derived umbilical cord mesenchymal stem cells (HDUMSC) and human-derived umbilical cord mesenchymal stem cells expressing erythropoietin (HDUMSC-EPO) to rescue total degenerated retina in a rat model.
Methods:
The study included four treatment groups, namely negative control using normal saline (HBSS) injection, positive control using sodium iodide 60 mg/kg (SI), SI treated with HDUMSC, and SI treated with HDUMSC-EPO given via subretinal and intravenous routes, to test the efficacy of retinal regeneration following SI-induced retinal degeneration. Retinal function in both phases was tested via electroretinography (ERG) and histological staining examining the outer nuclear layer (ONL).
Results:
There was a statistically significant result (P < 0.05) in the SI treated with HDUMSC-EPO only when comparing day 11 (mean = 23.6 μv), day 18 (mean = 25.2 μv), day 26 (mean = 26.3 μv), and day 32 (mean = 28.2 μv) to the b-wave ERG on day 4 rescue injection day (mean = 12.5 μv). The SI treated with HDUMSC-EPO showed significant improvement in b-wave ERG readings in the Sprague-Dawley (SD) rat but did not restore baseline readings prior to degeneration (day 0). Both treated groups' ONL thicknesses did not show significant changes compared to the negative control group (HBSS) following rescue therapy.
Conclusion:
Total retinal degeneration following intravenous SI injection was observed at 60 mg/kg. SI treated with HDUMSC and HDUMSC-EPO showed no regenerative potential compared to baseline in SI-induced total retina degeneration on ERG or histology, whereas SI treated with HDUMSC-EPO group showed a substantial increase in b-wave ERG amplitude over time.
... Mesenchymal stromal/stem cells (MSCs) are multipotent cells capable of differentiation into multiple cell types of mesenchymal and non-mesenchymal origin, including chondrocytes, osteoblasts, adipocytes, glial cells, neurons, epithelial cells and hepatocytes (e.g. pneumocytes, retinal pigment epithelium and renal tubular epithelial cells) [11][12][13][14][15][16][17][18] . MSCs can be isolated from bone marrow, adipose tissue, umbilical cord, Wharton's jelly, amniotic fluid, gingiva, tooth pulp, periodontal tissue and in general from connective tissue of most organs 13,14 . ...
Cell-based immunotherapies can provide safe and effective treatments for various disorders including autoimmunity, cancer, and excessive proinflammatory events in sepsis or viral infections. However, to achieve this goal there is a need for deeper understanding of mechanisms of the intercellular interactions. Regulatory T cells (Tregs) are a lymphocyte subset that maintain peripheral tolerance, whilst mesenchymal stem cells (MSCs) are multipotent nonhematopoietic progenitor cells. Despite coming from different origins, Tregs and MSCs share immunoregulatory properties that have been tested in clinical trials. Here we demonstrate how direct and indirect contact with allogenic MSCs improves Tregs’ potential for accumulation of immunosuppressive adenosine and suppression of conventional T cell proliferation, making them more potent therapeutic tools. Our results also demonstrate that direct communication between Tregs and MSCs is based on transfer of active mitochondria and fragments of plasma membrane from MSCs to Tregs, an event that is HLA-dependent and associates with HLA-C and HLA-DRB1 eplet mismatch load between Treg and MSC donors. Regulatory T (Treg) cells and mesenchymal stem cells (MSCs) are both cell populations capable of immune tolerance induction. Here the authors show that the transfer of mitochondria from mesenchymal stem cells to allogeneic Treg cells in an HLA-dependent manner results in enhanced immunosuppressive functions of Treg cells.
