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Keywords = regenerative ophthalmology

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36 pages, 2313 KiB  
Review
PLGA Implants for Controlled Drug Delivery and Regenerative Medicine: Advances, Challenges, and Clinical Potential
by Hossein Omidian and Renae L. Wilson
Pharmaceuticals 2025, 18(5), 631; https://doi.org/10.3390/ph18050631 - 27 Apr 2025
Cited by 1 | Viewed by 2306
Abstract
Poly(lactide-co-glycolide) (PLGA) implants have become a cornerstone in drug delivery and regenerative medicine due to their biocompatibility, tunable degradation, and capacity for sustained, localized therapeutic release. Recent innovations in polymer design, fabrication methods, and functional modifications have expanded their utility across [...] Read more.
Poly(lactide-co-glycolide) (PLGA) implants have become a cornerstone in drug delivery and regenerative medicine due to their biocompatibility, tunable degradation, and capacity for sustained, localized therapeutic release. Recent innovations in polymer design, fabrication methods, and functional modifications have expanded their utility across diverse clinical domains, including oncology, neurology, orthopedics, and ophthalmology. This review provides a comprehensive analysis of PLGA implant properties, fabrication strategies, and biomedical applications, while addressing key challenges such as burst release, incomplete drug release, manufacturing complexity, and inflammatory responses. Emerging solutions—such as 3D printing, in situ forming systems, predictive modeling, and patient-specific customization—are improving implant performance and clinical translation. Emphasis is placed on scalable production, long-term biocompatibility, and personalized design to support the next generation of precision therapeutics. Full article
(This article belongs to the Section Pharmaceutical Technology)
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22 pages, 2049 KiB  
Review
Stem Cell-Based Therapies for Glaucoma Treatment: A Review Bridging the Gap in Veterinary Patients
by Alícia de Sousa Moreira, Bruna Lopes, Ana Catarina Sousa, André Coelho, Patrícia Sousa, Ana Araújo, Esmeralda Delgado, Rui Alvites and Ana Colette Maurício
Int. J. Mol. Sci. 2025, 26(1), 232; https://doi.org/10.3390/ijms26010232 - 30 Dec 2024
Viewed by 2325
Abstract
Retinal diseases are characterized by progressive damage to retinal cells, leading to irreversible vision loss. Among these, glaucoma stands out as a multifactorial neurodegenerative disease involving elevated intraocular pressure, retinal ganglion cell apoptosis, and optic nerve damage, ultimately resulting in blindness in both [...] Read more.
Retinal diseases are characterized by progressive damage to retinal cells, leading to irreversible vision loss. Among these, glaucoma stands out as a multifactorial neurodegenerative disease involving elevated intraocular pressure, retinal ganglion cell apoptosis, and optic nerve damage, ultimately resulting in blindness in both humans and dogs. Stem cell-based therapies have emerged as a promising therapeutic option for such conditions due to their regenerative and neuroprotective potential. These therapies, particularly those based on mesenchymal stem cells, offer the potential to repair and protect retinal tissues through the bioactive molecules (growth factors, cytokines, chemokines) secreted, their secretome. However, research in this field, especially on the use of umbilical cord mesenchymal stem cells’ secretome, remains sparse. Most clinical trials focus on human glaucomatous patients, leaving a significant gap in veterinary patients’ application, especially in dogs, with additional research being needed to determine its usefulness in canine glaucoma treatment. Future studies should aim to evaluate these therapies across both human and veterinary contexts, broadening treatment possibilities for glaucoma. Full article
(This article belongs to the Special Issue Molecular Insight into Retinal Diseases)
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17 pages, 295 KiB  
Review
Innovative Bioscaffolds in Stem Cell and Regenerative Therapies for Corneal Pathologies
by Federico Visalli, Federico Fava, Matteo Capobianco, Mutali Musa, Fabiana D’Esposito, Andrea Russo, Davide Scollo, Antonio Longo, Caterina Gagliano and Marco Zeppieri
Bioengineering 2024, 11(9), 859; https://doi.org/10.3390/bioengineering11090859 - 23 Aug 2024
Cited by 2 | Viewed by 1400
Abstract
Corneal diseases, which can result in substantial visual impairment and loss of vision, are an important worldwide health issue. The aim of this review was to investigate the novel application of bioscaffolds in stem cell and regenerative treatments for the treatment of corneal [...] Read more.
Corneal diseases, which can result in substantial visual impairment and loss of vision, are an important worldwide health issue. The aim of this review was to investigate the novel application of bioscaffolds in stem cell and regenerative treatments for the treatment of corneal disorders. The current literature reports that organic and artificial substances create bioscaffolds that imitate the inherent structure of the cornea, facilitating the attachment, growth, and specialization of stem cells. Sophisticated methods such as electrospinning, 3D bioprinting, and surface modification have been reported to enhance the characteristics of the scaffold. These bioscaffolds have been shown to greatly improve the survival of stem cells and facilitate the regrowth of corneal tissue in both laboratory and live animal experiments. In addition, the incorporation of growth factors and bioactive compounds within the scaffolds can promote a favorable milieu for corneal regeneration. To summarize, the advancement of these groundbreaking bioscaffolds presents a hopeful treatment strategy for the regeneration of the cornea, which has the potential to enhance the results for individuals suffering from corneal disorders. This study highlights the possibility of utilizing the fields of biomaterials science and stem cell treatment to tackle medical demands that have not yet been satisfied in the field of ophthalmology. Full article
(This article belongs to the Special Issue Bioengineering and the Eye—2nd Edition)
23 pages, 1584 KiB  
Systematic Review
Bioengineering Human Upper Respiratory Mucosa: A Systematic Review of the State of the Art of Cell Culture Techniques
by Davaine Joel Ndongo Sonfack, Clémence Tanguay Boivin, Lydia Touzel Deschênes, Thibault Maurand, Célina Maguemoun, François Berthod, François Gros-Louis and Pierre-Olivier Champagne
Bioengineering 2024, 11(8), 826; https://doi.org/10.3390/bioengineering11080826 - 13 Aug 2024
Viewed by 2446
Abstract
Background: The upper respiratory mucosa plays a crucial role in both the physical integrity and immunological function of the respiratory tract. However, in certain situations such as infections, trauma, or surgery, it might sustain damage. Tissue engineering, a field of regenerative medicine, has [...] Read more.
Background: The upper respiratory mucosa plays a crucial role in both the physical integrity and immunological function of the respiratory tract. However, in certain situations such as infections, trauma, or surgery, it might sustain damage. Tissue engineering, a field of regenerative medicine, has found applications in various medical fields including but not limited to plastic surgery, ophthalmology, and urology. However, its application to the respiratory system remains somewhat difficult due to the complex morphology and histology of the upper respiratory tract. To date, a culture protocol for producing a handleable, well-differentiated nasal mucosa has yet to be developed. The objective of this review is to describe the current state of research pertaining to cell culture techniques used for producing autologous healthy human upper respiratory cells and mucosal tissues, as well as describe its clinical applications. Methods: A search of the relevant literature was carried out with no time restriction across Embase, Cochrane, PubMed, and Medline Ovid databases. Keywords related to “respiratory mucosa” and “culture techniques of the human airway” were the focus of the search strategy for this review. The risk of bias in retained studies was assessed using the Joanna Briggs Institute’s (JBI) critical appraisal tools for qualitative research. A narrative synthesis of our results was then conducted. Results: A total of 33 studies were included in this review, and thirteen of these focused solely on developing a cell culture protocol without further use. The rest of the studies used their own developed protocol for various applications such as cystic fibrosis, pharmacological, and viral research. One study was able to develop a promising model for nasal mucosa that could be employed as a replacement in nasotracheal reconstructive surgery. Conclusions: This systematic review extensively explored the current state of research regarding cell culture techniques for producing tissue-engineered nasal mucosa. Bioengineering the nasal mucosa holds great potential for clinical use. However, further research on mechanical properties is essential, as the comparison of engineered tissues is currently focused on morphology rather than comprehensive mechanical assessments. Full article
(This article belongs to the Section Regenerative Engineering)
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41 pages, 3571 KiB  
Review
Three-Dimensional Bioprinting: A Comprehensive Review for Applications in Tissue Engineering and Regenerative Medicine
by Nicholas A. Mirsky, Quinn T. Ehlen, Jason A. Greenfield, Michael Antonietti, Blaire V. Slavin, Vasudev Vivekanand Nayak, Daniel Pelaez, David T. Tse, Lukasz Witek, Sylvia Daunert and Paulo G. Coelho
Bioengineering 2024, 11(8), 777; https://doi.org/10.3390/bioengineering11080777 - 31 Jul 2024
Cited by 13 | Viewed by 9339
Abstract
Since three-dimensional (3D) bioprinting has emerged, it has continuously to evolved as a revolutionary technology in surgery, offering new paradigms for reconstructive and regenerative medical applications. This review highlights the integration of 3D printing, specifically bioprinting, across several surgical disciplines over the last [...] Read more.
Since three-dimensional (3D) bioprinting has emerged, it has continuously to evolved as a revolutionary technology in surgery, offering new paradigms for reconstructive and regenerative medical applications. This review highlights the integration of 3D printing, specifically bioprinting, across several surgical disciplines over the last five years. The methods employed encompass a review of recent literature focusing on innovations and applications of 3D-bioprinted tissues and/or organs. The findings reveal significant advances in the creation of complex, customized, multi-tissue constructs that mimic natural tissue characteristics, which are crucial for surgical interventions and patient-specific treatments. Despite the technological advances, the paper introduces and discusses several challenges that remain, such as the vascularization of bioprinted tissues, integration with the host tissue, and the long-term viability of bioprinted organs. The review concludes that while 3D bioprinting holds substantial promise for transforming surgical practices and enhancing patient outcomes, ongoing research, development, and a clear regulatory framework are essential to fully realize potential future clinical applications. Full article
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32 pages, 5807 KiB  
Review
The Third Dimension of Eye Care: A Comprehensive Review of 3D Printing in Ophthalmology
by Neil Lin, Maryse Gagnon and Kevin Y. Wu
Hardware 2024, 2(1), 1-32; https://doi.org/10.3390/hardware2010001 - 26 Jan 2024
Cited by 10 | Viewed by 5437
Abstract
Three-dimensional (3D) printing is a process in which materials are added together in a layer-by-layer manner to construct customized products. Many different techniques of 3D printing exist, which vary in materials used, cost, advantages, and drawbacks. Medicine is increasingly benefiting from this transformative [...] Read more.
Three-dimensional (3D) printing is a process in which materials are added together in a layer-by-layer manner to construct customized products. Many different techniques of 3D printing exist, which vary in materials used, cost, advantages, and drawbacks. Medicine is increasingly benefiting from this transformative technology, and the field of ophthalmology is no exception. The possible 3D printing applications in eyecare are vast and have been explored in the literature, such as 3D-printed ocular prosthetics, orbital implants, educational and anatomical models, as well as surgical planning and training. Novel drug-delivery platforms have also emerged because of 3D printing, offering improved treatment modalities for several ocular pathologies. Innovative research in 3D bioprinting of viable tissues, including the cornea, retina, and conjunctiva, is presenting an avenue for regenerative ophthalmic therapies in the future. Although further development in printing capabilities and suitable materials is required, 3D printing represents a powerful tool for enhancing eye health. Full article
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38 pages, 2180 KiB  
Review
Beyond Vision: An Overview of Regenerative Medicine and Its Current Applications in Ophthalmological Care
by Francisco J. Santa Cruz-Pavlovich, Andres J. Bolaños-Chang, Ximena I. Del Rio-Murillo, Guillermo A. Aranda-Preciado, Esmeralda M. Razura-Ruiz, Arturo Santos and Jose Navarro-Partida
Cells 2024, 13(2), 179; https://doi.org/10.3390/cells13020179 - 17 Jan 2024
Cited by 6 | Viewed by 4764
Abstract
Regenerative medicine (RM) has emerged as a promising and revolutionary solution to address a range of unmet needs in healthcare, including ophthalmology. Moreover, RM takes advantage of the body’s innate ability to repair and replace pathologically affected tissues. On the other hand, despite [...] Read more.
Regenerative medicine (RM) has emerged as a promising and revolutionary solution to address a range of unmet needs in healthcare, including ophthalmology. Moreover, RM takes advantage of the body’s innate ability to repair and replace pathologically affected tissues. On the other hand, despite its immense promise, RM faces challenges such as ethical concerns, host-related immune responses, and the need for additional scientific validation, among others. The primary aim of this review is to present a high-level overview of current strategies in the domain of RM (cell therapy, exosomes, scaffolds, in vivo reprogramming, organoids, and interspecies chimerism), centering around the field of ophthalmology. A search conducted on clinicaltrials.gov unveiled a total of at least 209 interventional trials related to RM within the ophthalmological field. Among these trials, there were numerous early-phase studies, including phase I, I/II, II, II/III, and III trials. Many of these studies demonstrate potential in addressing previously challenging and degenerative eye conditions, spanning from posterior segment pathologies like Age-related Macular Degeneration and Retinitis Pigmentosa to anterior structure diseases such as Dry Eye Disease and Limbal Stem Cell Deficiency. Notably, these therapeutic approaches offer tailored solutions specific to the underlying causes of each pathology, thus allowing for the hopeful possibility of bringing forth a treatment for ocular diseases that previously seemed incurable and significantly enhancing patients’ quality of life. As advancements in research and technology continue to unfold, future objectives should focus on ensuring the safety and prolonged viability of transplanted cells, devising efficient delivery techniques, etc. Full article
(This article belongs to the Special Issue Gene and Cell Therapy in Regenerative Medicine—Second Edition)
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17 pages, 4312 KiB  
Review
Current Advances in Corneal Stromal Stem Cell Biology and Therapeutic Applications
by Thomas Volatier, Claus Cursiefen and Maria Notara
Cells 2024, 13(2), 163; https://doi.org/10.3390/cells13020163 - 16 Jan 2024
Cited by 12 | Viewed by 4437
Abstract
Corneal stromal stem cells (CSSCs) are of particular interest in regenerative ophthalmology, offering a new therapeutic target for corneal injuries and diseases. This review provides a comprehensive examination of CSSCs, exploring their anatomy, functions, and role in maintaining corneal integrity. Molecular markers, wound [...] Read more.
Corneal stromal stem cells (CSSCs) are of particular interest in regenerative ophthalmology, offering a new therapeutic target for corneal injuries and diseases. This review provides a comprehensive examination of CSSCs, exploring their anatomy, functions, and role in maintaining corneal integrity. Molecular markers, wound healing mechanisms, and potential therapeutic applications are discussed. Global corneal blindness, especially in more resource-limited regions, underscores the need for innovative solutions. Challenges posed by corneal defects, emphasizing the urgent need for advanced therapeutic interventions, are discussed. The review places a spotlight on exosome therapy as a potential therapy. CSSC-derived exosomes exhibit significant potential for modulating inflammation, promoting tissue repair, and addressing corneal transparency. Additionally, the rejuvenation potential of CSSCs through epigenetic reprogramming adds to the evolving regenerative landscape. The imperative for clinical trials and human studies to seamlessly integrate these strategies into practice is emphasized. This points towards a future where CSSC-based therapies, particularly leveraging exosomes, play a central role in diversifying ophthalmic regenerative medicine. Full article
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18 pages, 6381 KiB  
Article
Matrix-Assisted Cell Transplantation for the Treatment of Limbal Stem Cell Deficiency in a Rabbit Model
by Yang Yu, Andrey Yurevich Andreev, Olga Sergeevna Rogovaya, Anastasia Mikhailovna Subbot, Sergey Petrovich Domogatsky, Sergey Eduardovich Avetisov, Ekaterina Andreevna Vorotelyak and Egor Olegovich Osidak
Biomedicines 2024, 12(1), 101; https://doi.org/10.3390/biomedicines12010101 - 3 Jan 2024
Cited by 10 | Viewed by 2165
Abstract
With the development of regenerative medicine in ophthalmology, the identification of cells with high proliferative potential in the limbal area has attracted the attention of ophthalmologists and offered a new option for treatment in clinical practice. Limbal stem cell deficiency (LSCD) is an [...] Read more.
With the development of regenerative medicine in ophthalmology, the identification of cells with high proliferative potential in the limbal area has attracted the attention of ophthalmologists and offered a new option for treatment in clinical practice. Limbal stem cell deficiency (LSCD) is an identified eye disease with a difficult and negative outcome, for which the traditional treatment is keratoplasty. This study sought to evaluate the efficacy of matrix-assisted cell transplantation consisting of in vitro-cultured autologous limbal stem cells (LSCs) and type I collagen for the treatment of LSCD in rabbits. LSCD was induced in 10 rabbits by a combination of mechanical limbectomy and alkali burns. Cells were cultured on a plate for 14 days before being transferred to a collagen-based matrix for another 7 days. Rabbits were divided into two groups as follows: the experimental group (five rabbits) received matrix-assisted cell transplantation, while the control group (five rabbits) received only conservative therapy with anti-inflammatory eye drops. During the postoperative period, all rabbits were examined using slit-lamp biomicroscopy with photo-registration and fluorescent staining, impression cytology and anterior segment optical coherence tomography (AS-OCT). Rabbits were euthanized at 30 and 120 days, and their corneas were processed for histology and immunohistochemistry. As a consequence, rabbits in the experimental group demonstrated the restoration of the corneal epithelium and transparency without epithelial defects. Moreover, goblet cells were absent in the central zone of the corneal epithelium. In conclusion, our new method of treatment enhanced the corneal surface and is an effective method of treatment for LSCD in rabbits. Full article
(This article belongs to the Section Biomedical Engineering and Materials)
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15 pages, 1752 KiB  
Review
NLRP3 Inflammasome as a Potentially New Therapeutic Target of Mesenchymal Stem Cells and Their Exosomes in the Treatment of Inflammatory Eye Diseases
by Carl Randall Harrell, Valentin Djonov, Ana Antonijevic and Vladislav Volarevic
Cells 2023, 12(18), 2327; https://doi.org/10.3390/cells12182327 - 21 Sep 2023
Cited by 11 | Viewed by 3153
Abstract
Due to their potent immunoregulatory and angio-modulatory properties, mesenchymal stem cells (MSCs) and their exosomes (MSC-Exos) have emerged as potential game-changers in regenerative ophthalmology, particularly for the personalized treatment of inflammatory diseases. MSCs suppress detrimental immune responses in the eyes and alleviate ongoing [...] Read more.
Due to their potent immunoregulatory and angio-modulatory properties, mesenchymal stem cells (MSCs) and their exosomes (MSC-Exos) have emerged as potential game-changers in regenerative ophthalmology, particularly for the personalized treatment of inflammatory diseases. MSCs suppress detrimental immune responses in the eyes and alleviate ongoing inflammation in ocular tissues by modulating the phenotype and function of all immune cells that play pathogenic roles in the development and progression of inflammatory eye diseases. MSC-Exos, due to their nano-sized dimension and lipid envelope, easily bypass all barriers in the eyes and deliver MSC-sourced bioactive compounds directly to target cells. Although MSCs and their exosomes offer a novel approach to treating immune cell-driven eye diseases, further research is needed to optimize their therapeutic efficacy. A significant number of experimental studies is currently focused on the delineation of intracellular targets, which crucially contribute to the immunosuppressive and anti-inflammatory effects of MSCs and MSC-Exos. The activation of NLRP3 inflammasome induces programmed cell death of epithelial cells, induces the generation of inflammatory phenotypes in eye-infiltrated immune cells, and enhances the expression of adhesion molecules on ECs facilitating the recruitment of circulating leukocytes in injured and inflamed eyes. In this review article, we summarize current knowledge about signaling pathways that are responsible for NLRP3 inflammasome-driven intraocular inflammation and we emphasize molecular mechanisms that regulate MSC-based modulation of NLRP3-driven signaling in eye-infiltrated immune cells, providing evidence that NLRP3 inflammasome should be considered a potentially new therapeutic target for MSCs and MSC-Exo-based treatment of inflammatory eye diseases. Full article
(This article belongs to the Special Issue Updates on Mesenchymal Stem Cells-Derived Extracellular Vesicles)
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20 pages, 2722 KiB  
Article
Effects of Rho-Associated Kinase (Rock) Inhibitors (Alternative to Y-27632) on Primary Human Corneal Endothelial Cells
by Gary S. L. Peh, Francisco Bandeira, Dawn Neo, Khadijah Adnan, Yossa Hartono, Hon Shing Ong, Sacha Naso, Anandalakshmi Venkatraman, José A. P. Gomes, Viridiana Kocaba and Jodhbir S. Mehta
Cells 2023, 12(9), 1307; https://doi.org/10.3390/cells12091307 - 3 May 2023
Cited by 11 | Viewed by 3921
Abstract
(1) Rho-associated coiled-coil protein kinase (ROCK) signaling cascade impacts a wide array of cellular events. For cellular therapeutics, scalable expansion of primary human corneal endothelial cells (CECs) is crucial, and the inhibition of ROCK signaling using a well characterized ROCK inhibitor (ROCKi) Y-27632 [...] Read more.
(1) Rho-associated coiled-coil protein kinase (ROCK) signaling cascade impacts a wide array of cellular events. For cellular therapeutics, scalable expansion of primary human corneal endothelial cells (CECs) is crucial, and the inhibition of ROCK signaling using a well characterized ROCK inhibitor (ROCKi) Y-27632 had been shown to enhance overall endothelial cell yield. (2) In this study, we compared several classes of ROCK inhibitors to both ROCK-I and ROCK-II, using in silico binding simulation. We then evaluated nine ROCK inhibitors for their effects on primary CECs, before narrowing it down to the two most efficacious compounds—AR-13324 (Netarsudil) and its active metabolite, AR-13503—and assessed their impact on cellular proliferation in vitro. Finally, we evaluated the use of AR-13324 on the regenerative capacity of donor cornea with an ex vivo corneal wound closure model. Donor-matched control groups supplemented with Y-27632 were used for comparative analyses. (3) Our in silico simulation revealed that most of the compounds had stronger binding strength than Y-27632. Most of the nine ROCK inhibitors assessed worked within the concentrations of between 100 nM to 30 µM, with comparable adherence to that of Y-27632. Of note, both AR-13324 and AR-13503 showed better cellular adherence when compared to Y-27632. Similarly, the proliferation rates of CECs exposed to AR-13324 were comparable to those of Y-27632. Interestingly, CECs expanded in a medium supplemented with AR-13503 were significantly more proliferative in (i) untreated vs. AR-13503 (1 μM; * p < 0.05); (ii) untreated vs. AR-13503 (10 μM; *** p < 0.001); (iii) Y-27632 vs. AR-13503 (10 μM; ** p < 0.005); (iv) AR-13324 (1 μM) vs. AR-13503 (10 μM; ** p < 0.005); and (v) AR-13324 (0.1 μM) vs. AR-13503 (10 μM; * p < 0.05). Lastly, an ex vivo corneal wound healing study showed a comparable wound healing rate for the final healed area in corneas exposed to Y-27632 or AR-13324. (4) In conclusion, we were able to demonstrate that various classes of ROCKi compounds other than Y-27632 were able to exert positive effects on primary CECs, and systematic donor-match controlled comparisons revealed that the FDA-approved ROCK inhibitor, AR-13324, is a potential candidate for cellular therapeutics or as an adjunct drug in regenerative treatment for corneal endothelial diseases in humans. Full article
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14 pages, 1493 KiB  
Article
Early Visibility of Cellular Aggregates and Changes in Central Corneal Thickness as Predictors of Successful Corneal Endothelial Cell Injection Therapy
by Evan N. Wong, Valencia H. X. Foo, Gary S. L. Peh, Hla M. Htoon, Heng-Pei Ang, Belinda Y. L. Tan, Hon-Shing Ong and Jodhbir S. Mehta
Cells 2023, 12(8), 1167; https://doi.org/10.3390/cells12081167 - 15 Apr 2023
Cited by 2 | Viewed by 2340
Abstract
(1) Background: Cell injection therapy is an emerging treatment for bullous keratopathy (BK). Anterior segment optical coherence tomography (AS-OCT) imaging allows the high-resolution assessment of the anterior chamber. Our study aimed to investigate the predictive value of the visibility of cellular aggregates for [...] Read more.
(1) Background: Cell injection therapy is an emerging treatment for bullous keratopathy (BK). Anterior segment optical coherence tomography (AS-OCT) imaging allows the high-resolution assessment of the anterior chamber. Our study aimed to investigate the predictive value of the visibility of cellular aggregates for corneal deturgescence in an animal model of bullous keratopathy. (2) Methods: Cell injections of corneal endothelial cells were performed in 45 eyes in a rabbit model of BK. AS-OCT imaging and central corneal thickness (CCT) measurement were performed at baseline and on day 1, day 4, day 7 and day 14 following cell injection. A logistic regression was modelled to predict successful corneal deturgescence and its failure with cell aggregate visibility and CCT. Receiver-operating characteristic (ROC) curves were plotted, and areas under the curve (AUC) calculated for each time point in these models. (3) Results: Cellular aggregates were identified on days 1, 4, 7 and 14 in 86.7%, 39.5%, 20.0% and 4.4% of eyes, respectively. The positive predictive value of cellular aggregate visibility for successful corneal deturgescence was 71.8%, 64.7%, 66.7% and 100.0% at each time point, respectively. Using logistic regression modelling, the visibility of cellular aggregates on day 1 appeared to increase the likelihood of successful corneal deturgescence, but this did not reach statistical significance. An increase in pachymetry, however, resulted in a small but statistically significant decreased likelihood of success, with an odds ratio of 0.996 for days 1 (95% CI 0.993–1.000), 2 (95% CI 0.993–0.999) and 14 (95% CI 0.994–0.998) and an odds ratio of 0.994 (95% CI 0.991–0.998) for day 7. The ROC curves were plotted, and the AUC values were 0.72 (95% CI 0.55–0.89), 0.80 (95% CI 0. 62–0.98), 0.86 (95% CI 0.71–1.00) and 0.90 (95% CI 0.80–0.99) for days 1, 4, 7 and 14, respectively. (4) Conclusions: Logistic regression modelling of cell aggregate visibility and CCT was predictive of successful corneal endothelial cell injection therapy. Full article
(This article belongs to the Special Issue Advances in Allogeneic Cell Therapy)
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13 pages, 2278 KiB  
Article
Corneal Reconstruction with EGFP-Labelled Limbal Mesenchymal Stem Cells in a Rabbit Model of Limbal Stem Cell Deficiency
by Julia I. Khorolskaya, Daria A. Perepletchikova, Kirill E. Zhurenkov, Daniel V. Kachkin, Aleksandr A. Rubel, Miralda I. Blinova and Natalia A. Mikhailova
Int. J. Mol. Sci. 2023, 24(6), 5431; https://doi.org/10.3390/ijms24065431 - 12 Mar 2023
Cited by 4 | Viewed by 3096
Abstract
Ocular surface reconstruction is essential for treating corneal epithelial defects and vision recovery. Stem cell-based therapy demonstrates promising results but requires further research to elucidate stem cell survival, growth, and differentiation after transplantation in vivo. This study examined the corneal reconstruction promoted by [...] Read more.
Ocular surface reconstruction is essential for treating corneal epithelial defects and vision recovery. Stem cell-based therapy demonstrates promising results but requires further research to elucidate stem cell survival, growth, and differentiation after transplantation in vivo. This study examined the corneal reconstruction promoted by EGFP-labeled limbal mesenchymal stem cells (L-MSCs-EGFP) and their fate after transplantation. EGFP labeling allowed us to evaluate the migration and survival rates of the transferred cells. L-MSCs-EGFP seeded onto decellularized human amniotic membrane (dHAM) were transplanted into rabbits with a modeled limbal stem cell deficiency. The localization and viability of the transplanted cells in animal tissue were analyzed using histology, immunohistochemistry, and confocal microscopy up to 3 months after transplantation. EGFP-labeled cells remained viable for the first 14 days after transplantation. By the 90th day, epithelialization of the rabbit corneas reached 90%, but the presence of viable labeled cells was not observed within the newly formed epithelium. Although labeled cells demonstrated low survivability in host tissue, the squamous corneal-like epithelium was partially restored by the 30th day after transplantation of the tissue-engineered graft. Overall, this study paves the way for further optimization of transplantation conditions and studying the mechanisms of corneal tissue restoration. Full article
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16 pages, 424 KiB  
Review
Adipose Stem Cells in Modern-Day Ophthalmology
by Mutali Musa, Marco Zeppieri, Ehimare S. Enaholo, Carlo Salati and Pier Camillo Parodi
Clin. Pract. 2023, 13(1), 230-245; https://doi.org/10.3390/clinpract13010021 - 4 Feb 2023
Cited by 7 | Viewed by 3315
Abstract
Stem cells (SCs) have evolved as an interesting and viable factor in ophthalmologic patient care in the past decades. SCs have been classified as either embryonic, mesenchymal, tissue-specific, or induced pluripotent cells. Multiple novel management techniques and clinical trials have been established to [...] Read more.
Stem cells (SCs) have evolved as an interesting and viable factor in ophthalmologic patient care in the past decades. SCs have been classified as either embryonic, mesenchymal, tissue-specific, or induced pluripotent cells. Multiple novel management techniques and clinical trials have been established to date. While available publications are predominantly animal-model-based, significant material is derived from human studies and case-selected scenarios. This possibility of explanting cells from viable tissue to regenerate/repair damaged tissue points to an exciting future of therapeutic options in all fields of medicine, and ophthalmology is surely not left out. Adipose tissue obtained from lipo-aspirates has been shown to produce mesenchymal SCs that are potentially useful in different body parts, including the oculo-visual system. An overview of the anatomy, physiology, and extraction process for adipose-tissue-derived stem cells (ADSC) is important for better understanding the potential therapeutic benefits. This review examines published data on ADSCs in immune-modulatory, therapeutic, and regenerative treatments. We also look at the future of ADSC applications for ophthalmic patient care. The adverse effects of this relatively novel therapy are also discussed. Full article
(This article belongs to the Special Issue 2022 Feature Papers in Clinics and Practice)
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18 pages, 4582 KiB  
Article
Derivation of Limbal Stem Cells from Human Adult Mesenchymal Stem Cells for the Treatment of Limbal Stem Cell Deficiency
by Marta Cadenas-Martin, Francisco Arnalich-Montiel and Maria P De Miguel
Int. J. Mol. Sci. 2023, 24(3), 2350; https://doi.org/10.3390/ijms24032350 - 25 Jan 2023
Cited by 3 | Viewed by 3229
Abstract
Approximately 10 million individuals have blindness due to limbal stem cell (LSCs) deficiency, one of the most challenging problems in ophthalmology. To replenish the LSC pool, an autologous extraocular cell source is appropriate, thereby avoiding the risk of immune rejection, the need for [...] Read more.
Approximately 10 million individuals have blindness due to limbal stem cell (LSCs) deficiency, one of the most challenging problems in ophthalmology. To replenish the LSC pool, an autologous extraocular cell source is appropriate, thereby avoiding the risk of immune rejection, the need for immunosuppression and the risk of damaging the contralateral eye. In recent years, adipose-derived mesenchymal stem cells (ADSCs) have been a key element in ocular regenerative medicine. In this study, we developed a protocol for deriving human LSCs from ADSCs compatible with the standard carrier human amniotic membrane, helping provide a stem cell pool capable of maintaining proper corneal epithelial homeostasis. The best protocol included an ectodermal induction step by culturing ADSCs with media containing fetal bovine serum, transforming growth factor-β inhibitor SB-505124, Wnt inhibitor IWP-2 and FGF2 for 7 days, followed by an LSC induction step of culture in modified supplemental hormonal epithelial medium supplemented with pigment epithelium-derived factor and keratinocyte growth factor for 10 additional days. The optimal differentiation efficiency was achieved when cells were cultured in this manner over vitronectin coating, resulting in up to 50% double-positive αp63/BMI-1 cells. The results of this project will benefit patients with LSC deficiency, aiding the restoration of vision. Full article
(This article belongs to the Special Issue Advance in Mesenchymal Stem Cells)
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