Transplantation of miPSC/mESC-derived retinal ganglion cells into healthy and glaucomatous retinas

Molecular Therapy: Methods & Clinical Development

Petr Baranov¹  Evgenii Kegeles²  Pavel Volchkov²  Julia Oswald³  Tomas Minelli³ 

[1] Research Institute of Personalized Medicine, National Center for Personalized Medicine of Endocrine Diseases, The National Medical Research Center for Endocrinology, Moscow 117036, Russia;Life Sciences Research Center, Moscow Institute of Physics and Technology, Dolgoprudniy 141700, Russia;The Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA;

关键词: cell replacement therapies;    retina;    retinal ganglion cells;    transplantation;    organoids;    glaucoma;   

DOI  :  

来源: DOAJ

【 摘 要 】

Optic neuropathies, including glaucoma, are a group of neurodegenerative diseases, characterized by the progressive loss of retinal ganglion cells (RGCs), leading to irreversible vision loss. While previous studies demonstrated the potential to replace RGCs with primary neurons from developing mouse retinas, their use is limited clinically. We demonstrate successful transplantation of mouse induced pluripotent stem cell (miPSC)/mouse embryonic stem cell (mESC)-derived RGCs into healthy and glaucomatous mouse retinas, at a success rate exceeding 65% and a donor cell survival window of up to 12 months. Transplanted Thy1-GFP+ RGCs were able to polarize within the host retina and formed axonal processes that followed host axons along the retinal surface and entered the optic nerve head. RNA sequencing of donor RGCs re-isolated from host retinas at 24 h and 1 week post-transplantation showed upregulation of cellular pathways mediating axonal outgrowth, extension, and guidance. Additionally, we provide evidence of subtype-specific diversity within miPSC-derived RGCs prior to transplantation.

【 授权许可】

Unknown