Magnetically steered cell therapy for reduction of intraocular pressure as a treatment strategy for open-angle glaucoma
Trabecular meshwork (TM) cell therapy has been proposed as a next-generation treatment for elevated intraocular pressure (IOP) in glaucoma, the most common cause of irreversible blindness. Using a magnetic cell steering technique with excellent efficiency and tissue-specific targeting, we delivered...
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eLife Sciences Publications Ltd
2025-07-01
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| Online Access: | https://elifesciences.org/articles/103256 |
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| author | M Reza Bahranifard Jessica Chan A Thomas Read Guorong Li Lin Cheng Babak N Safa Seyed Mohammad Siadat Anamik Jhunjhunwala Hans E Grossniklaus Stanislav Y Emelianov W Daniel Stamer Markus H Kuehn C Ross Ethier |
| author_facet | M Reza Bahranifard Jessica Chan A Thomas Read Guorong Li Lin Cheng Babak N Safa Seyed Mohammad Siadat Anamik Jhunjhunwala Hans E Grossniklaus Stanislav Y Emelianov W Daniel Stamer Markus H Kuehn C Ross Ethier |
| author_sort | M Reza Bahranifard |
| collection | DOAJ |
| description | Trabecular meshwork (TM) cell therapy has been proposed as a next-generation treatment for elevated intraocular pressure (IOP) in glaucoma, the most common cause of irreversible blindness. Using a magnetic cell steering technique with excellent efficiency and tissue-specific targeting, we delivered two types of cells into a mouse model of glaucoma: either human adipose-derived mesenchymal stem cells (hAMSCs) or induced pluripotent cell derivatives (iPSC-TM cells). We observed a 4.5 [3.1, 6.0] mmHg or 27% reduction in intraocular pressure (IOP) for 9 months after a single dose of only 1500 magnetically steered hAMSCs, explained by increased outflow through the conventional pathway and associated with a higher TM cellularity. iPSC-TM cells were also effective, but less so, showing only a 1.9 [0.4, 3.3] mmHg or 13% IOP reduction and increased risk of tumorigenicity. In both cases, injected cells remained detectable in the iridocorneal angle 3 weeks post-transplantation. Based on the locations of the delivered cells, the mechanism of IOP lowering is most likely paracrine signaling. We conclude that magnetically steered hAMSC cell therapy has potential for long-term treatment of ocular hypertension in glaucoma. |
| format | Article |
| id | doaj-art-2ec8925cf7c14a5ca6a41ceea9625bf4 |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-2ec8925cf7c14a5ca6a41ceea9625bf42025-08-20T02:44:17ZengeLife Sciences Publications LtdeLife2050-084X2025-07-011310.7554/eLife.103256Magnetically steered cell therapy for reduction of intraocular pressure as a treatment strategy for open-angle glaucomaM Reza Bahranifard0https://orcid.org/0009-0005-1369-8772Jessica Chan1A Thomas Read2https://orcid.org/0000-0002-2764-6413Guorong Li3https://orcid.org/0009-0002-4047-8546Lin Cheng4Babak N Safa5https://orcid.org/0000-0002-1849-2870Seyed Mohammad Siadat6https://orcid.org/0000-0002-5063-0305Anamik Jhunjhunwala7https://orcid.org/0000-0002-7126-4463Hans E Grossniklaus8Stanislav Y Emelianov9W Daniel Stamer10https://orcid.org/0000-0002-2504-8997Markus H Kuehn11C Ross Ethier12https://orcid.org/0000-0001-6110-3052Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, United StatesSchool of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, United StatesWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, United StatesDepartment of Ophthalmology, Duke University, Durham, United StatesDepartment of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, United States; Veterans Administration Center for the Prevention and Treatment of Visual Loss, Iowa City VA Healthcare System, Iowa City, United StatesWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, United States; Department of Medical Engineering, University of South Florida, Tampa, United StatesWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, United StatesWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, United StatesDepartments of Ophthalmology and Pathology, Emory University School of Medicine, Atlanta, United StatesWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, United States; School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, United StatesDepartment of Ophthalmology, Duke University, Durham, United States; Department of Biomedical Engineering, Duke University, Durham, United StatesDepartment of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, United States; Veterans Administration Center for the Prevention and Treatment of Visual Loss, Iowa City VA Healthcare System, Iowa City, United StatesWoodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, United States; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, United StatesTrabecular meshwork (TM) cell therapy has been proposed as a next-generation treatment for elevated intraocular pressure (IOP) in glaucoma, the most common cause of irreversible blindness. Using a magnetic cell steering technique with excellent efficiency and tissue-specific targeting, we delivered two types of cells into a mouse model of glaucoma: either human adipose-derived mesenchymal stem cells (hAMSCs) or induced pluripotent cell derivatives (iPSC-TM cells). We observed a 4.5 [3.1, 6.0] mmHg or 27% reduction in intraocular pressure (IOP) for 9 months after a single dose of only 1500 magnetically steered hAMSCs, explained by increased outflow through the conventional pathway and associated with a higher TM cellularity. iPSC-TM cells were also effective, but less so, showing only a 1.9 [0.4, 3.3] mmHg or 13% IOP reduction and increased risk of tumorigenicity. In both cases, injected cells remained detectable in the iridocorneal angle 3 weeks post-transplantation. Based on the locations of the delivered cells, the mechanism of IOP lowering is most likely paracrine signaling. We conclude that magnetically steered hAMSC cell therapy has potential for long-term treatment of ocular hypertension in glaucoma.https://elifesciences.org/articles/103256glaucomastem cellintraocular pressuremouse |
| spellingShingle | M Reza Bahranifard Jessica Chan A Thomas Read Guorong Li Lin Cheng Babak N Safa Seyed Mohammad Siadat Anamik Jhunjhunwala Hans E Grossniklaus Stanislav Y Emelianov W Daniel Stamer Markus H Kuehn C Ross Ethier Magnetically steered cell therapy for reduction of intraocular pressure as a treatment strategy for open-angle glaucoma eLife glaucoma stem cell intraocular pressure mouse |
| title | Magnetically steered cell therapy for reduction of intraocular pressure as a treatment strategy for open-angle glaucoma |
| title_full | Magnetically steered cell therapy for reduction of intraocular pressure as a treatment strategy for open-angle glaucoma |
| title_fullStr | Magnetically steered cell therapy for reduction of intraocular pressure as a treatment strategy for open-angle glaucoma |
| title_full_unstemmed | Magnetically steered cell therapy for reduction of intraocular pressure as a treatment strategy for open-angle glaucoma |
| title_short | Magnetically steered cell therapy for reduction of intraocular pressure as a treatment strategy for open-angle glaucoma |
| title_sort | magnetically steered cell therapy for reduction of intraocular pressure as a treatment strategy for open angle glaucoma |
| topic | glaucoma stem cell intraocular pressure mouse |
| url | https://elifesciences.org/articles/103256 |
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