Magnetic attraction of iron-endocytosed corneal endothelial cells to Descemet's membrane

Mimura, Tatsuya; Shimomura, Naoki; Usui, Tomohiro; Noda, Yasuo; Kaji, Yuichi; Yamgami, Satoru; Amano, Shiro; Miyata, Kazunori; Araie, Makoto

doi:10.1016/s0014-4835(03)00057-5

Cited by 95 publications

(73 citation statements)

References 14 publications

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“…A second strategy is to inject cultured CECs in the form of a cell suspension into the anterior chamber (cell-based therapy). [23][24][25][26] However, if the injected CECs do not spontaneously adhere to the posterior corneal surface of the recipient, the reconstruction of a corneal endothelium will fail. In 2009, we found that the selective ROCK inhibitor, Y-27632, promotes CEC adhesion to a substrate, enhances CEC proliferation, and suppresses CEC apoptosis, 13 and our subsequent reports confirm these findings and reveal the underlying mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Effect of a p38 Mitogen-Activated Protein Kinase Inhibitor on Corneal Endothelial Cell Proliferation

Nakahara

Okumura

Nakano

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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Citation: Nakahara M, Okumura N, Nakano S, Koizumi N. Effect of a p38 mitogen-activated protein kinase inhibitor on corneal endothelial cell proliferation. Invest Ophthalmol Vis Sci. 2018;59:4218-4227. https:// doi.org/10.1167/iovs.18-24394 PURPOSE. We have performed clinical research on cell-based therapy for corneal endothelial decompensation since 2013. The purpose of this study was to investigate the usefulness of a p38 MAPK inhibitor for promoting proliferation of human corneal endothelial cells (HCECs).METHODS. HCECs were cultured in media supplemented with various low-molecular-weight compounds to screen for the effect of those compounds on cell proliferation. Activation of substrates of p38 MAPK and cell cycle regulatory proteins were evaluated by western blotting. Corneal endothelial wounds were created in a rabbit model, and p38 MAPK was applied in eye drop form, followed by evaluation of cell proliferation in the corneal endothelium by Ki67-immunostaining. RESULTS.HCECs cultured with SB203580 exhibited hexagonal morphology and similar size and morphology, whereas control HCECs cultured without inhibitor exhibited monolayer morphology and varied in size and morphology. Flow cytometry demonstrated that cell proliferation was significantly increased by SB203580. Western blotting showed activation of ATF2 and HSP27 (substrates of p38 MAPK), and upregulation of cyclin D and downregulation of p27 were induced by inhibiting p38 MAPK. In the rabbit model, promotion of wound healing of the corneal endothelium was associated with significant upregulation of Ki67-positive proliferating cells following topical administration of SB203580 when compared with untreated endothelium (50.9% and 36.1%, respectively).CONCLUSIONS. Activation of p38 MAPK signaling due to culture stress might suppress the proliferation of HCECs, whereas a p38 MAPK inhibitor can counteract this activation and enable efficient in vitro HCEC expansion.

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Section: Discussionmentioning

confidence: 99%

Effect of a p38 Mitogen-Activated Protein Kinase Inhibitor on Corneal Endothelial Cell Proliferation

Nakahara

Okumura

Nakano

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…Mimura transplanted iron-endocytozing cultured CECs with magnetic attraction to treat CEC defects. The drawback to this technique is that hemosiderosis might occur after the injection of ironendocytozing CECs [10,25]. Bi attempted to use superparamagnetic iron oxide nanoparticle cell labeling to assist with HCEC transplantation by attaching the posterior corneal stroma in ex vivo animal models, but this has not been used for transplants in vivo [26].…”

Section: Fig 9 Histological Examination 4 Months After Transplantatmentioning

confidence: 99%

Targeted Transplantation of Human Umbilical Cord Blood Endothelial Progenitor Cells with Immunomagnetic Nanoparticles to Repair Corneal Endothelium Defect

Shao

Chen

et al. 2015

Stem Cells and Development

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Corneal endothelial dysfunction involves progressive corneal edema and loss of visual acuity, which result in the need for corneal transplantation. The global shortage of donor corneas limits the development of the surgery. Reconstruction of a bioengineered corneal endothelium might resolve this problem. Various scaffolds have been used, but poor biocompatibility and degradation limit their applications. In this study, a novel method of targeted cellular transplantation without permanent residence of cell carriers in the host was proposed. Human umbilical cord blood endothelial progenitor cells (UCB EPCs) were labeled with CD34 immunomagnetic nanoparticles. The efficiency of the magnet attraction was evaluated in vitro with a simple device simulating the anterior chamber. The UCB EPCs labeled with nanoparticles were transplanted into the anterior chamber of rabbits with magnet attraction. The results indicated that labeling the nanoparticles did not affect the proliferation of the UCB EPCs. The in vitro study indicated that the magnet could directionally attract UCB EPCs labeled with nanoparticles. The in vivo study indicated that the corneas in rabbits transplanted with UCB EPCs labeled with nanoparticles and magnet attraction became relatively transparent with little edema. These results showed that UCB EPCs labeled with CD34 immunomagnetic nanoparticles could be attracted directionally by a magnet and could repair corneal endothelial defects, providing a promising cell therapy for corneal endothelial dysfunction.

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“…Prior literature suggests that moving these cells in a magnetic field may represent an interesting approach. For example, after incorporating raw iron filings, rabbit corneal endothelial cells were transplanted into a rabbit model of endothelial cell dysfunction, and localized successfully to the cornea, with disappearance of edema [115,116]. In an ex-vivo transplant model, HCECs were loaded with magnetite oxide superparamagnetic particles (SPMs) onto human corneas in the presence of an external magnetic field [117].…”

Section: Cell Replacement Therapies To Treat Corneal Endotheliummentioning

confidence: 99%

Regenerative Cell Therapy for Corneal Endothelium

Bartáková

Kunzevitzky

Goldberg

2014

Curr Ophthalmol Rep

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Endothelial cell dysfunction as in Fuchs dystrophy or pseudophakic bullous keratopathy, and the limited regenerative capacity of human corneal endothelial cells (HCECs), drive the need for corneal transplant. In response to limited donor corneal availability, significant effort has been directed towards cell therapy as an alternative to surgery. Stimulation of endogenous progenitors, or transplant of stem cell-derived HCECs or in vitro-expanded, donor-derived HCECs could replace traditional surgery with regenerative therapy. Ex vivo expansion of HCECs is technically challenging, and the basis for molecular identification of functional HCECs is not established. Delivery of cells to the inner layer of the human cornea is another challenge: different techniques, from simple injection to artificial corneal scaffolds, are being investigated. Despite remaining questions, corneal endothelial cell therapies, translated to the clinic, represent the future for the treatment of corneal endotheliopathies.

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Magnetic attraction of iron-endocytosed corneal endothelial cells to Descemet's membrane

Cited by 95 publications

References 14 publications

Effect of a p38 Mitogen-Activated Protein Kinase Inhibitor on Corneal Endothelial Cell Proliferation

Effect of a p38 Mitogen-Activated Protein Kinase Inhibitor on Corneal Endothelial Cell Proliferation

Targeted Transplantation of Human Umbilical Cord Blood Endothelial Progenitor Cells with Immunomagnetic Nanoparticles to Repair Corneal Endothelium Defect

Regenerative Cell Therapy for Corneal Endothelium

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