Human-Induced Pluripotent Stem Cells-Derived Corneal Endothelial-Like Cells Promote Corneal Transparency in a Rabbit Model of Bullous Keratopathy

Sun, Baoqi; Bikkuzin, Timur; Li, Xuran; Shi, Yan; Zhang, Hong

doi:10.1089/scd.2020.0205

Cited by 8 publications

(10 citation statements)

References 27 publications

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“…Meanwhile, additional candidates for adjunctive therapy are being investigated, such as fibroblast grow factor 1 derivatives which may promote endothelial proliferation and migration [61,62], and other preclinical studies use cells that will not require corneal donation, such as human SC from embryonic [63], induced pluripotent [64–67], umbilical cord-derived [68], dental pulp [69] and eyelid hair follicle-derived [70] sources. None of these approaches are currently in human trials.…”

Section: Endotheliummentioning

confidence: 99%

Recent advances in cell-based regenerative therapies for corneal disease

Kaufman

Jun

2023

Current Opinion in Ophthalmology

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Purpose of reviewWith limited access of more than half the world's population to corneal transplantation, regenerative medicine may represent a promising alternative. This review explores the main advancements achieved in cell-based therapies for corneal epithelium, stroma, and endothelium during 2021--2022. Recent findingsMultiple surgical techniques have been developed for epithelial limbal stem cell replacement. Recent studies aimed to gain greater understanding and characterization of these techniques. Though no clear superiority could be demonstrated, simple limbal epithelial transplantation seems to have the most clinical and cost effectiveness. For stromal disease, autologous adipose-derived stem cells have shown favorable results. For endothelial dysfunction, the validity of intracameral cultivated allogeneic endothelial cell injection and Descemetorrhexis without endothelial keratoplasty, as well as the benefits of adjunctive rho-associated kinase inhibitors, were emphasized. SummaryA plethora of innovative cell-based regenerative therapies for corneal diseases have been developed in past years. While recent literature solidifies our knowledge, most studies are still in preliminary or preclinical stages. Though showing great promise, these approaches will require larger studies with betterdefined endpoints to establish their benefits over currently available treatments.

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Section: Endotheliummentioning

confidence: 99%

Recent advances in cell-based regenerative therapies for corneal disease

Kaufman

Jun

2023

Current Opinion in Ophthalmology

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“…As technology in this field continues to advance, commercially available reprogramming kits such as the CytoTune-iPS Sendai Reprogramming kit (Thermo Fisher Scientific, Waltham, MA, USA) [57][58][59][60] utilize Sendai particles to deliver the Yamanaka factors into somatic cells, reprogramming them into iPSCs. The second approach involves the direct induction of CECs from human iPS cell lines, which can now be obtained commercially (Applied StemCell-ASC, ATCC) or through orga-nizations supporting iPS cell research (Center for iPS Cell Research and Application-CiRA Foundation, European Bank for induced pluripotent Stem Cells-EBiSC) [61][62][63][64]. There are also clinical-grade iPS cell lines available that follow strict GMP guidelines and comply with FDA regulations [64].…”

Section: Progression In the Technologymentioning

confidence: 99%

“…In that study, the use of serum was replaced with a chemically defined lipid concentrate [62]. Similar approaches include the use of knock-out serum replacement in addition to inhibitors or activators of specific pathways such as DKK-2 (Wnt inhibitor), SB-431542, CHIR-99021 [58][59][60]63,82], or a combination of small molecules such as A-769662 (AMPK activator) and AT-13148 (Akt inhibitor) [82]. Hatou et al described an induction approach to directly differentiate iPSCs by regulating the gene expression levels of C-JUN, C-FOS, NR3C2, and SOX9 using a combination of optimized cytokines in a chemically defined, animal and human origin-free corneal endothelial differentiation medium (CEDM) [61].…”

Section: Differentiation From Nccs To Cecsmentioning

confidence: 99%

Corneal Endothelial-like Cells Derived from Induced Pluripotent Stem Cells for Cell Therapy

Peh

Yam

et al. 2023

IJMS

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Corneal endothelial dysfunction is one of the leading causes of corneal blindness, and the current conventional treatment option is corneal transplantation using a cadaveric donor cornea. However, there is a global shortage of suitable donor graft material, necessitating the exploration of novel therapeutic approaches. A stem cell-based regenerative medicine approach using induced pluripotent stem cells (iPSCs) offers a promising solution, as they possess self-renewal capabilities, can be derived from adult somatic cells, and can be differentiated into all cell types including corneal endothelial cells (CECs). This review discusses the progress and challenges in developing protocols to induce iPSCs into CECs, focusing on the different media formulations used to differentiate iPSCs to neural crest cells (NCCs) and subsequently to CECs, as well as the characterization methods and markers that define iPSC-derived CECs. The hurdles and solutions for the clinical application of iPSC-derived cell therapy are also addressed, including the establishment of protocols that adhere to good manufacturing practice (GMP) guidelines. The potential risks of genetic mutations in iPSC-derived CECs associated with long-term in vitro culture and the danger of potential tumorigenicity following transplantation are evaluated. In all, this review provides insights into the advancement and obstacles of using iPSC in the treatment of corneal endothelial dysfunction.

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“…Although the majority of human pluripotent stem cell (hPSC)-based studies previously used hESCs, the field is moving towards the use of hiPSC, as they avoid the ethical issues of embryo destruction and can be used worldwide [21]. hiPSC-derived cells also have the potential to be autologous in nature, circumventing the issue of immunological rejection by the host [15 ▪ ,16 ▪ ,22,23].…”

Section: Highlights From Four Recent Animal Studiesmentioning

confidence: 99%

Cell therapy in corneal endothelial disease

Wong

2022

Current Opinion in Ophthalmology

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Purpose of reviewEndothelial keratoplasty is the current gold standard for treating corneal endothelial diseases, achieving excellent visual outcomes and rapid rehabilitation. There are, however, severe limitations to donor tissue supply and uneven access to surgical teams and facilities across the globe. Cell therapy is an exciting approach that has shown promising early results. Herein, we review the latest developments in cell therapy for corneal endothelial disease.Recent findingsWe highlight the work of several groups that have reported successful functional outcomes of cell therapy in animal models, with the utilization of human embryonic stem cells, human-induced pluripotent stem cells and cadaveric human corneal endothelial cells (CECs) to generate populations of CECs for intracameral injection. The use of corneal endothelial progenitors, viability of cryopreserved cells and efficacy of simple noncultured cells, in treating corneal decompensation is of particular interest. Further additions to the collective understanding of CEC physiology, and the process of cultivating and administering effective cell therapy are reviewed as well.SummaryThe latest developments in cell therapy for corneal endothelial disease are presented. The continuous growth in this field gives rise to the hope that a viable solution to the large numbers of corneal blind around the world will one day be reality.

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Human-Induced Pluripotent Stem Cells-Derived Corneal Endothelial-Like Cells Promote Corneal Transparency in a Rabbit Model of Bullous Keratopathy

Cited by 8 publications

References 27 publications

Recent advances in cell-based regenerative therapies for corneal disease

Recent advances in cell-based regenerative therapies for corneal disease

Corneal Endothelial-like Cells Derived from Induced Pluripotent Stem Cells for Cell Therapy

Cell therapy in corneal endothelial disease

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