Progress of iPS cell-based transplantation therapy for retinal diseases

Akiba, Ryutaro; Takahashi, Masayo; Baba, Takayuki; Mandai, Michiko

doi:10.1007/s10384-022-00974-5

Cited by 6 publications

(5 citation statements)

References 52 publications

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“…Compared to RPE cell suspension, RPE patches can be easily delivered to a target area in retina and the cells on patches are in a form close to their native configuration with tight junction formed [ 7 , 11 ]. Several literature reported RPE sheets used for clinical transplantation.…”

Section: Discussionmentioning

confidence: 99%

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Tissue engineering RPE sheet derived from hiPSC-RPE cell spheroids supplemented with Y-27632 and RepSox

Wang,

Yang,

Chen

et al. 2024

J Biol Eng

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Background Retinal pigment epithelium (RPE) cell therapy is a promising way to treat many retinal diseases. However, obtaining transplantable RPE cells is time-consuming and less effective. This study aimed to develop novel strategies for generating engineered RPE patches with physiological characteristics. Results Our findings revealed that RPE cells derived from human induced pluripotent stem cells (hiPSCs) successfully self-assembled into spheroids. The RPE spheroids treated with Y27632 and Repsox had increased expression of epithelial markers and RPE-specific genes, along with improved cell viability and barrier function. Transcriptome analysis indicated enhanced cell adhesion and extracellular matrix (ECM) organization in RPE spheroids. These RPE spheroids could be seeded and bioprinted on collagen vitrigel (CV) membranes to construct engineered RPE sheets. Circular RPE patches, obtained by trephining a specific section of the RPE sheet, exhibited abundant microvilli and pigment particles, as well as reduced proliferative capacity and enhanced maturation. Conclusions Our study suggests that the supplementation of small molecules and 3D spheroid culture, as well as the bioprinting technique, can be effective methods to promote RPE cultivation and construct engineered RPE sheets, which may support future clinical RPE cell therapy and the development of RPE models for research applications.

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Section: Discussionmentioning

confidence: 99%

“…Clinical-grade and qualified hiPSC-RPE must exhibit a polarized and mature phenotype, possess a functional barrier and display low proliferative capacity to mitigate the risk of tumorigenicity [ 9 , 10 ]. Besides, there is a need for improved production efficiency, as the current methods are often time-consuming [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Tissue engineering RPE sheet derived from hiPSC-RPE cell spheroids supplemented with Y-27632 and RepSox

Wang,

Yang,

Chen

et al. 2024

J Biol Eng

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“…In 2014, these became the first such cells in the world to undergo clinical research. In these treatments, the patient’s stem cells are differentiated outside the body into cells with the desired function, cultured, and then transplanted into the patient’s tissues to restore that function [ 42 ]. By using the patient’s cells, rejection after transplantation can be suppressed, but not all cells can be used.…”

Section: Mrna-based Protein Supplementation For Regenerative Medicinementioning

confidence: 99%

Cell Reprogramming and Differentiation Utilizing Messenger RNA for Regenerative Medicine

Inagaki

2023

JDB

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The COVID-19 pandemic generated interest in the medicinal applications of messenger RNA (mRNA). It is expected that mRNA will be applied, not only to vaccines, but also to regenerative medicine. The purity of mRNA is important for its medicinal applications. However, the current mRNA synthesis techniques exhibit problems, including the contamination of undesired 5′-uncapped mRNA and double-stranded RNA. Recently, our group developed a completely capped mRNA synthesis technology that contributes to the progress of mRNA research. The introduction of chemically modified nucleosides, such as N1-methylpseudouridine and 5-methylcytidine, has been reported by Karikó and Weissman, opening a path for the practical application of mRNA for vaccines and regenerative medicine. Yamanaka reported the production of induced pluripotent stem cells (iPSCs) by introducing four types of genes using a retrovirus vector. iPSCs are widely used for research on regenerative medicine and the preparation of disease models to screen new drug candidates. Among the Yamanaka factors, Klf4 and c-Myc are oncogenes, and there is a risk of tumor development if these are integrated into genomic DNA. Therefore, regenerative medicine using mRNA, which poses no risk of genome insertion, has attracted attention. In this review, the author summarizes techniques for synthesizing mRNA and its application in regenerative medicine.

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“…Treatment decisions will become multi-faceted and personalized. Using human iPSC derivatives for transplantation is a way to avoid or reduce the risk of autoimmune rejection, as these cells can be derived from patient samples [ 94 , 95 ]. However, the clinical application of human iPSCs and organoids is contentious, related to the tumorigenicity and heterogeneity of iPSCs, as well as the absence of standardized culture protocols, such as viability and batch effect of iPSC-derived cells or organoids.…”

Section: Challenges In the Clinical Application Of Ipscs And Organoidsmentioning

confidence: 99%

Application of patient-derived induced pluripotent stem cells and organoids in inherited retinal diseases

Liang,

Sun,

Duan

et al. 2023

Stem Cell Res Ther

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Inherited retinal diseases (IRDs) can induce severe sight-threatening retinal degeneration and impose a considerable economic burden on patients and society, making efforts to cure blindness imperative. Transgenic animals mimicking human genetic diseases have long been used as a primary research tool to decipher the underlying pathogenesis, but there are still some obvious limitations. As an alternative strategy, patient-derived induced pluripotent stem cells (iPSCs), particularly three-dimensional (3D) organoid technology, are considered a promising platform for modeling different forms of IRDs, including retinitis pigmentosa, Leber congenital amaurosis, X-linked recessive retinoschisis, Batten disease, achromatopsia, and best vitelliform macular dystrophy. Here, this paper focuses on the status of patient-derived iPSCs and organoids in IRDs in recent years concerning disease modeling and therapeutic exploration, along with potential challenges for translating laboratory research to clinical application. Finally, the importance of human iPSCs and organoids in combination with emerging technologies such as multi-omics integration analysis, 3D bioprinting, or microfluidic chip platform are highlighted. Patient-derived retinal organoids may be a preferred choice for more accurately uncovering the mechanisms of human retinal diseases and will contribute to clinical practice.

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Progress of iPS cell-based transplantation therapy for retinal diseases

Cited by 6 publications

References 52 publications

Tissue engineering RPE sheet derived from hiPSC-RPE cell spheroids supplemented with Y-27632 and RepSox

Tissue engineering RPE sheet derived from hiPSC-RPE cell spheroids supplemented with Y-27632 and RepSox

Cell Reprogramming and Differentiation Utilizing Messenger RNA for Regenerative Medicine

Application of patient-derived induced pluripotent stem cells and organoids in inherited retinal diseases

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