scholarly journals Human Stem Cell Transplantation for Retinal Degenerative Diseases. Where Are We Now?

Medicina ◽  
2022 ◽  
Vol 58 (1) ◽  
pp. 102
Author(s):  
Ignacio Alcalde ◽  
Cristina Sánchez-Fernández ◽  
Carla Martín ◽  
Nagore De Pablo ◽  
Nahla Jemni-Damer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Degenerative Diseases ◽  
Age Related ◽  
Retinal Degenerative Diseases

Background and Objectives: Irreversible visual impairment is mainly caused by retinal degenerative diseases such as age-related macular degeneration and retinitis pigmentosa. Stem cell research has experienced rapid progress in recent years, and researchers and clinical ophthalmologists are trying to implement this promising technology to treat retinal degeneration. The objective of this systematic review is to analyze currently available data from clinical trials applying stem cells to treat human retinal diseases. Materials and Methods: We performed a systematic literature search in PubMed to identify articles related with stem cell therapies to retinal diseases published prior to September 2021. Furthermore, a systematic search in ClinicalTrials (NIH U.S. National Library of Medicine) was performed to identify clinical trials using stem cells to treat retinal diseases. A descriptive analysis of status, conditions, phases, interventions, and outcomes is presented here. Conclusions: To date, no available therapy based on stem cell transplantation is approved for use with patients. However, numerous clinical trials are currently finishing their initial phases and, in general, the outcomes related to implantation techniques and their long-term safety seem promising. In the next few years, we expect to see quantifiable results pertaining to visual function improvement.

scholarly journals Perspectives of Stem Cell–Based Therapy for Age-Related Retinal Degenerative Diseases

2017 ◽  
Vol 26 (9) ◽  
pp. 1538-1541 ◽  
Author(s):  
Vladimir Holan ◽  
Barbora Hermankova ◽  
Jan Kossl
Keyword(s):  
Stem Cell ◽  
Treatment Protocol ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
Cell Type ◽  
Retinal Cells ◽  
Cell Based Therapy ◽  
Age Related ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases, which include age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and glaucoma, mostly affect the elderly population and are the most common cause of decreased quality of vision or even blindness. So far, there is no satisfactory treatment protocol to prevent, stop, or cure these disorders. A great hope and promise for patients suffering from retinal diseases is represented by stem cell–based therapy that could replace diseased or missing retinal cells and support regeneration. In this respect, mesenchymal stem cells (MSCs) that can be obtained from the particular patient and used as autologous cells have turned out to be a promising stem cell type for treatment. Here we show that MSCs can differentiate into cells expressing markers of retinal cells, inhibit production of pro-inflammatory cytokines by retinal tissue, and produce a number of growth and neuroprotective factors for retinal regeneration. All of these properties make MSCs a prospective cell type for cell-based therapy of age-related retinal degenerative diseases.

Stem Cell Based Treatment Strategies for Degenerative Diseases of the Retina

2021 ◽  
Vol 16 ◽  
Author(s):  
Deepthi Rajendran Nair ◽  
Biju Thomas
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Degenerative Diseases ◽  
Retinal Degenerative Diseases ◽  
Pigment Epithelial Cells

Background: The main cause of progressive vision impairment in retinal degenerative diseases is the dysfunction of photoreceptors and the underlying retinal pigment epithelial cells. The inadequate regenerative capacity of the neural retina and lack of established therapeutic options demand the development of clinical grade protocols to halt degenerative process in the eye or to replace the damaged cells by using stem cell derived products. Recently, stem cell-based regenerative therapies are at the forefront of clinical investigations for retinal dystrophies. Objective: This article will review different stem cell-based therapies currently employed for retinal degenerative diseases, recent clinical trials, and major challenges in the translation of these therapies from bench to bedside. Methodology: A systematic literature review was carried out to identify potentially relevant articles published in MEDLINE/PubMed, Embase, ClinicalTrials.gov, Drugs@FDA, European Medicines Agency, World Health Organization International Clinical Trials Registry Platform and CENTRAL Result: Transplantation of healthy cells to replace the damaged cells in the outer retina is a clinically relevant concept because the inner retina that communicates with the visual areas of the brain remains functional even after the photoreceptors are completely lost. Different methods have been established for the differentiation of pluripotent stem cells into different retinal cell types that can be used for therapies. Factors released from transplanted somatic stem cells showed trophic support and photoreceptor rescue during early stages of the disease. Several preclinical and phase I/II clinical studies using terminally differentiated photoreceptor/ retinal pigment epithelial cells derived from pluripotent stem cells have shown proof of concept for visual restoration in Age-related macular degeneration (AMD), Stargardt disease and Retinitis pigmentosa (RP). Conclusion: Cell replacement therapy has great potential for vision restoration. The results obtained from the initial clinical trials are encouraging and indicates its therapeutic benefits. The current status of the therapies suggests that there is a long way to go before these results can be applied to routine clinical practice. Input from the ongoing multicentre clinical trials will give a more refined idea for the future design of clinical- grade protocols to transplant GMP level HLA matched cells.

Resolving Ethical Issues in Stem Cell Clinical Trials: The Example of Parkinson Disease

2010 ◽  
Vol 38 (2) ◽  
pp. 257-266 ◽  
Author(s):  
Bernard Lo ◽  
Lindsay Parham
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Parkinson Disease ◽  
Cell Transplantation ◽  
Ethical Issues ◽  
Current Therapy ◽  
Pluripotent Cells ◽  
Cord Injury

Stem cells derived from pluripotent cells offer the hope of new treatments for diseases for which current therapy is inadequate. Clinical trials are essential in developing effective and safe stem cell therapies and fulfilling this promise. However, such clinical trials raise ethical issues that are more complex than those raised in clinical trials using drugs, cord blood stem cells, or adult stem cells. Several clinical trials are now being carried out with stem cells derived from pluripotent cells, and many more can be expected in light of the rapid scientific progress in the field.Degenerative neurological diseases are desirable targets for stem cell clinical trials. The FDA has approved Phase 1 clinical trials of neural stem cell transplantation for Batten Disease, Pelizaeus-Merzbacher Disease, and spinal cord injury. In Parkinson Disease (PD), stem cell transplantation could correct the primary pathophysiological defect — inadequate levels of the neurotransmitter dopamine. Current treatment is unsatisfactory in late-stage PD.

scholarly journals Trends of Stem Cell Therapies in Age-Related Macular Degeneration

2021 ◽  
Vol 10 (8) ◽  
pp. 1785
Author(s):  
Tadao Maeda ◽  
Sunao Sugita ◽  
Yasuo Kurimoto ◽  
Masayo Takahashi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Macular Degeneration ◽  
Cell Transplantation ◽  
New Technologies ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Stem Cell Therapies ◽  
Cell Therapies ◽  
Age Related

Age-related macular degeneration (AMD) is a highly prevalent irreversible impairment in the elderly population worldwide. Stem cell therapies have been considered potentially viable for treating AMD through the direct replacement of degenerated cells or secretion of trophic factors that facilitate the survival of existing cells. Among them, the safety of pluripotent stem cell-derived retinal pigment epithelial (RPE) cell transplantation against AMD, and some hereditary retinal degenerative diseases, has been discussed to a certain extent in clinical studies of RPE cell transplantation. Preparations are in progress for its clinical application. On the other hand, clinical trials using somatic stem cells are also being conducted, though these had controversial outcomes. Retinal regenerative medicine using stem cells is expected to make steady progress toward practical use while new technologies are incorporated from various fields, thereby making the role of ophthalmologists in this field increasingly important.

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

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 588
Author(s):  
Vladimir Holan ◽  
Katerina Palacka ◽  
Barbora Hermankova
Keyword(s):  
Clinical Trials ◽  
Experimental Studies ◽  
Experimental Models ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
Retinal Cells ◽  
Cell Based Therapy ◽  
Age Related ◽  
Retinal Degenerative Diseases

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.

scholarly journals Advancement in Nanostructure-Based Tissue-Engineered Biomaterials for Retinal Degenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1005
Author(s):  
Sonali Suresh Rohiwal ◽  
Zdenka Ellederová ◽  
Taras Ardan ◽  
Jiri Klima
Keyword(s):  
Stem Cells ◽  
Retinal Degeneration ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Subretinal Space ◽  
Retinal Diseases ◽  
Degenerative Diseases ◽  
Retinal Cells ◽  
Wide Range ◽  
Retinal Degenerative Diseases

The review intends to overview a wide range of nanostructured natural, synthetic and biological membrane implants for tissue engineering to help in retinal degenerative diseases. Herein, we discuss the transplantation strategies and the new development of material in combination with cells such as induced pluripotent stem cells (iPSC), mature retinal cells, adult stem cells, retinal progenitors, fetal retinal cells, or retinal pigment epithelial (RPE) sheets, etc. to be delivered into the subretinal space. Retinitis pigmentosa and age-related macular degeneration (AMD) are the most common retinal diseases resulting in vision impairment or blindness by permanent loss in photoreceptor cells. Currently, there are no therapies that can repair permanent vision loss, and the available treatments can only delay the advancement of retinal degeneration. The delivery of cell-based nanostructure scaffolds has been presented to enrich cell survival and direct cell differentiation in a range of retinal degenerative models. In this review, we sum up the research findings on different types of nanostructure scaffolds/substrate or material-based implants, with or without cells, used to deliver into the subretinal space for retinal diseases. Though, clinical and pre-clinical trials are still needed for these transplants to be used as a clinical treatment method for retinal degeneration.

Gene and Induced Pluripotent Stem Cell Therapy for Retinal Diseases

2019 ◽  
Vol 20 (1) ◽  
pp. 201-216 ◽  
Author(s):  
Akiko Maeda ◽  
Michiko Mandai ◽  
Masayo Takahashi
Keyword(s):  
Stem Cell ◽  
Retinitis Pigmentosa ◽  
Visual Information ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
Age Related ◽  
Retinal Degenerative Diseases ◽  
Induced Pluripotent

Given the importance of visual information to many daily activities, retinal degenerative diseases—which include both inherited conditions (such as retinitis pigmentosa) and acquired conditions (such as age-related macular degeneration)—can have a dramatic impact on human lives. The therapeutic options for these diseases remain limited. Since the discovery of the first causal gene for retinitis pigmentosa almost three decades ago, more than 250 genes have been identified, and gene therapies have been rapidly developed. Simultaneously, stem cell technologies such as induced pluripotent stem cell–based transplantation have advanced and have been applied to the treatment of retinal degenerative diseases. Here, we review recent progress in these expanding fields and discuss the potential for precision medicine in ophthalmic care.

scholarly journals Advancing a Stem Cell Therapy for Age-Related Macular Degeneration

2020 ◽  
Vol 15 (2) ◽  
pp. 89-97 ◽  
Author(s):  
Helen C. O’Neill ◽  
Ioannis J. Limnios ◽  
Nigel L. Barnett
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Cell Therapy ◽  
Macular Degeneration ◽  
Cell Transplantation ◽  
Stem Cell Therapy ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Age Related

The retinal pigment epithelium (RPE) is a multifunctional monolayer located at the back of the eye required for the survival and function of the light-sensing photoreceptors. In Age-related Macular Degeneration (AMD), the loss of RPE cells leads to photoreceptor death and permanent blindness. RPE cell transplantation aims to halt or reverse vision loss by preventing the death of photoreceptor cells and is considered one of the most viable applications of stem cell therapy in the field of regenerative medicine. Proof-of-concept of RPE cell transplantation for treating retinal degenerative disease, such as AMD, has long been established in animal models and humans using primary RPE cells, while recent research has focused on the transplantation of RPE cells derived from human pluripotent stem cells (hPSC). Early results from clinical trials indicate that transplantation of hPSC-derived RPE cells is safe and can improve vision in AMD patients. Current hPSC-RPE cell production protocols used in clinical trials are nevertheless inefficient. Treatment of large numbers of AMD patients using stem cellderived products may be dependent on the ability to generate functional cells from multiple hPSC lines using robust and clinically-compliant methods. Transplantation outcomes may be improved by delivering RPE cells on a thin porous membrane for better integration into the retina, and by manipulation of the outcome through control of immune rejection and inflammatory responses.

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