Retinal Organoids from Induced Pluripotent Stem Cells of Patients with Inherited Retinal Diseases: A Systematic Review DOI Creative Commons
Yoo Jin Lee, Dong Hyun Jo

Stem Cell Reviews and Reports, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 18, 2024

Abstract Background Currently, most inherited retinal diseases lack curative interventions, and available treatment modalities are constrained to symptomatic approaches. Retinal organoid technology has emerged as a method for treating diseases, with growing academic interest in recent years. The purpose of this review was systematically organize the current protocols generating organoids using induced pluripotent stem cells from patients disease investigate application research. Methods Data were collected PubMed, Scopus, Web Science databases keyword search. main search term used “retinal organoid,” accompanied by secondary keywords such “optic cup,” “three-dimensional,” “self-organizing.” final conducted on October 2, 2024. Results Of 2,129 studies retrieved, 130 included qualitative synthesis. generation research use five major approaches, categorized into 3D combination 2D/3D implemented modifications. Disease phenotypes have been successfully reproduced via individuals facilitating progression novel therapeutic developments. Cells obtained cell therapy, progress toward their potential integration clinical practice is underway. Considering applications, shown promise across various domains. Conclusion In systematic review, we organized diseases. applications including modeling, screening therapies, replacement therapy. Further advancements would make clinically significant tool Graphical

Language: Английский

Human-based complex in vitro models: their promise and potential for rare disease therapeutics DOI Creative Commons
Surat Parvatam, Francesca Pistollato, Lindsay J. Marshall

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 27, 2025

Rare diseases affect a small percentage of an individual country’s population; however, with over 7,000 in total, rare represent significant disease burden impacting up to 10% the world’s population. Despite this, there are no approved treatments for almost 95% diseases, and existing cost-intensive patients. More than 70% genetic nature, patient-specific mutations. This calls need have personalised preclinical models that can lead effective, speedy, affordable therapeutic options. Complex vitro (CIVMs), including those using induced pluripotent stem cells (iPSCs), organoids, organs-on-chips emerging as powerful human-based pre-clinical systems capacity provide efficacy data enabling drugs move into clinical trials. In this narrative review, we discuss how CIVMs providing insights biomedical research on diseases. We also these being used trials develop Finally, propose recommendations human relevant could be leveraged increase translatability basic, applied nonclinical outcomes field therapeutics developed well middle-and low-income countries.

Language: Английский

Citations

0
Innovative approaches to treatment of eye diseases: advances in stem cell therapy use in ophthalmology DOI

Victor Oluwatomiwa Ajekiigbe,

Chinonyelum Emmanuel Agbo,

Ikponmwosa Jude Ogieuhi

et al.

International Ophthalmology, Journal Year: 2025, Volume and Issue: 45(1)

Published: March 22, 2025

Language: Английский

Citations

0
Retinal Organoids: Innovative Tools for Understanding Retinal Degeneration DOI Open Access
Nadia Galindo‐Cabello, Estefanía Caballano‐Infantes, Gregorio Benites

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3263 - 3263

Published: April 1, 2025

Retinal degenerative diseases (RDDs) comprise diverse genetic and phenotypic conditions that cause progressive retinal dysfunction cell loss, leading to vision impairment or blindness. Most RDDs lack appropriate animal models for their study, which affects understanding disease mechanisms delays the progress of new treatment development. Recent advances in stem engineering, omics, organoid technology are facilitating research into there no previously existing models. The development organoids produced from human cells has impacted study as well vitro diseases, opening possibilities applications regenerative medicine, drug discovery, precision medicine. In this review, we recapitulate RDD, mentioning some main pathways underlying neurodegeneration can be studied these models, limitations future challenges rapidly advancing field.

Language: Английский

Citations

0
CRB1 mutations cause structural and molecular defects in patient-derived retinal pigment epithelium cells DOI
Yini Wang, Yuqin Liang,

Yalan Zhou

et al.

Experimental Eye Research, Journal Year: 2025, Volume and Issue: unknown, P. 110445 - 110445

Published: May 1, 2025

Language: Английский

Citations

0
The application of retinal organoids in ophthalmic regenerative medicine: A mini-review DOI Creative Commons

Xinmei Lan,

Huixia Jiang,

Qian Wang

et al.

Regenerative Therapy, Journal Year: 2024, Volume and Issue: 26, P. 382 - 386

Published: June 1, 2024

Retinal organoids are three-dimensional (3D) microscopic tissues that induced and differentiated from stem cells or progenitor in vitro have a highly similar structure to the retina. With optimization development of 3D retinal culture system improvement differentiation technology, broad application prospects development, regenerative medicine, biomaterial evaluation, disease mechanism investigation, drug screening. In this review we summarize recent their applications ophthalmic medicine. particular, highlight promise challenges use modeling discovery.

Language: Английский

Citations

2
Clinical exome analysis and targeted gene repair of the c.1354dupT variant in iPSC lines from patients with PROM1-related retinopathies exhibiting diverse phenotypes DOI Creative Commons
Kevin Puertas‐Neyra, Rosa M. Coco,

Leticia Hernández‐Rodríguez

et al.

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 2, 2024

Abstract Background Inherited retinal dystrophies (IRD) are one of the main causes incurable blindness worldwide. IRD caused by mutations in genes that encode essential proteins for retina, leading to photoreceptor degeneration and loss visual function. generates an enormous global financial burden due lack understanding a significant part its pathophysiology, molecular diagnosis, near absence non-palliative treatment options. Patient-derived induced pluripotent stem cells (iPSC) seem be excellent option addressing these questions, serving as exceptional tools in-depth studies pathophysiology testing new therapeutic approaches. Methods From cohort 8 patients with PROM1 -related IRD, we identified 3 carrying same variant (c.1354dupT) but expressing three different phenotypes: Cone rod dystrophy (CORD), Retinitis pigmentosa (RP), Stargardt disease type 4 (STGD4). These target patients, along healthy relative from each, underwent comprehensive ophthalmic examinations their genetic panel study was expanded through clinical exome sequencing (CES). Subsequently, non-integrative patient-derived iPSC were generated fully characterized. Correction c.1354dupT mutation performed using CRISPR/Cas9, restoration gene confirmed flow cytometry western blotting lines. Results CES revealed 2 presented monoallelic variants associated complement system or differentiation peroxisome biogenesis disorders, respectively. The pluripotency functionality lines confirmed, correction restored capability encoding Prominin-1 (CD133) genetically repaired Conclusions is distinct AR phenotypes IRD. This pleotropic effect might related influence other dystrophies. However, further evidence needs provided. Future experiments should include gene-edited potential modelling elucidate this matter question. Graphical

Language: Английский

Citations

2
Comparative analysis of regulations and studies on stem cell therapies: focusing on induced pluripotent stem cell (iPSC)-based treatments DOI Creative Commons

Sang Yun Song,

Yoojun Nam,

Yeri Alice Rim

et al.

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 21, 2024

Abstract Stem cell therapies have emerged as a promising approach in regenerative medicine, demonstrating potential personalized disease modeling, and drug discovery. Therapies based on induced pluripotent stem cells (iPSCs) particularly stand out for their ability to differentiate into various types while avoiding ethical concerns. However, the development application of these are influenced by varying regulatory frameworks across countries. This study provides comparative analysis regulations research key regions: The European Union (EU), Switzerland, South Korea, Japan, United States. First, reviews therapies. EU Switzerland maintain rigorous guidelines that prioritize safety considerations, which can hinder innovation. In contrast, States adopts more flexible stance, facilitating rapid Korea Japan take balanced incorporating practices from both regimes. These differences reflect each country’s unique priorities impact pace scope therapy development. Moreover, examines global trends clinical trials treatments data obtained two sources: ClinicalTrials.gov ICTRP. Findings indicate significant growth number since 2008, involving iPSCs. Therapeutic studies iPSCs predominantly target conditions affecting cardiovascular nervous systems considered vital. results put emphasis treatments. Meanwhile, such also varies country. where relatively adopted, leading position. countries fall behind with imposed. reflects need guidance active findings underscore importance legal innovation ensuring safety. Regulatory agencies different should collaborate achieve standard ensure safe efficient advancement Global convergence will promote international collaboration applicability new

Language: Английский

Citations

2
Anesthetic effects on electrophysiological responses across the visual pathway DOI Creative Commons
Shiyao Zhang,

Weihui Xu,

Shanshan Liu

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 13, 2024

Anesthetics are widely used in electrophysiological tests to assess retinal and visual system functions avoid experimental errors caused by movement stress animals. To determine the most suitable anesthetic for tests, excluding ketamine chloral hydrate due regulatory side effect concerns, this study investigated effects of ethyl carbamate (EC), avertin (AR), pentobarbital sodium (PS) on signal conduction retina primary cortex. Assessments included flash electroretinogram (FERG), pattern (PERG), evoked potentials (PVEP), (FVEP), FERG FVEP were evaluate responses cortex stimuli, respectively, while PERG PVEP assessed stimuli. The research showed that AR demonstrates least disruption pathway, as evidenced consistently high characteristic peaks group across various tests. In contrast, mice given EC exhibited lowest peak values both FVEP, subjects anesthetized with PS suppressed oscillatory responses. Notably, substantial observed only AR. Consequently, among three anesthetics tested, is studies.

Language: Английский

Citations

1
Evaluation of mesenchymal stem cells as an in vitro model for inherited retinal diseases DOI Creative Commons

Maria S. Dodina,

Dzerassa Gurtsieva, Alexander Karabelsky

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Nov. 15, 2024

Retinal pathologies are major causes of vision impairment and blindness in humans, inherited retinal diseases (IRDs), such as retinitis pigmentosa, Leber congenital amaurosis, Stargardt disease, greatly contribute to this problem. In vitro disease modeling can be used for understanding the development pathology screening therapeutic pharmaceutical compounds. preclinical research phase, models complement vivo by reducing animal studies, decreasing costs, shortening timelines. Additionally, may not always accurately replicate human phenotype. This review examines types cells that create IRD models, including retina-specific cell lines, primary cells, induced pluripotent stem (iPSCs), more. Special attention is given mesenchymal (MSCs), which characterized various isolation sources, relative ease isolation, straightforward differentiation. MSCs derived from bone marrow (BM), adipose tissue (AT), dental (DT), umbilical cord (UC), other sources differentiate into photoreceptor pigment epithelial (RPE) dysfunction most commonly associated with IRDs. Subsequent differentiation carried out via methods: culturing induction media supplemented certain growth factors, co-culturing or their conditioned media, regulating gene expression viral vector-delivered transcription factors (TFs) microRNAs (miRNAs). Compared popular iPSCs, example, MSC-based significantly cheaper faster obtain, making them more feasible large-scale drug screening. Nevertheless, existing methods need further optimization promising platform receive success it deserves.

Language: Английский

Citations

0
Patient-derived induced pluripotent stem cells with a MERTK mutation exhibit cell junction abnormalities and aberrant cellular differentiation potential DOI Creative Commons
Hang Zhang,

Ling-Zi Wu,

Zhenyu Liu

et al.

World Journal of Stem Cells, Journal Year: 2024, Volume and Issue: 16(5), P. 512 - 524

Published: May 23, 2024

Human induced pluripotent stem cell (hiPSC) technology is a valuable tool for generating patient-specific cells, facilitating disease modeling, and investigating mechanisms. However, iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics.

Language: Английский

Citations

0