Transplantation of Retinal Ganglion Cells Derived from Male Germline Stem Cell as a Potential Treatment to Glaucoma
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AbstractGlaucoma is characterized by retinal ganglion cell (RGC) degeneration and is the second leading cause of blindness worldwide. However, current treatments such as eye drop or surgery have limitations and do not target the loss of RGC. Regenerative therapy using embryonic stem cells (ESCs) holds a promising option, but ethical concern hinders clinical applications on human subjects. In this study, we employed spermatogonial stem cells (SSCs) as an alternative source of ESCs for cell-based regenerative therapy in mouse glaucoma model. We generated functional RGCs from SSCs with a two-step protocol without applying viral transfection or chemical induction. SSCs were first dedifferentiated to embryonic stem-like cells (SSC-ESCs) that resemble ESCs in morphology, gene expression signatures, and stem cell properties. The SSC-ESCs then differentiated toward retinal lineages. We showed SSC-ESC-derived retinal cells expressed RGC-specific marker Brn3b and functioned as bona fide RGCs. To allow in vivo RGC tracing, Brn3b-EGFP reporter SSC-ESCs were generated and the derived RGCs were subsequently transplanted into the retina of glaucoma mouse models by intravitreal injection. We demonstrated that the transplanted RGCs could survive in host retina for at least 10 days after transplantation. SSC-ESC-derived RGCs can thus potentially be a novel alternative to replace the damaged RGCs in glaucomatous retina.
Acceptance Date03/10/2019
All Author(s) ListSUEN Hoi Ching, QIAN Yan, LIAO Jinyue, LUK Chun Shui, LEE Wing Tung, NG Kin Wing Judy, CHAN Ting Hei Thomas, HOU Hei Wan, LI Ingrid, LI Kit, CHAN Wai-Yee, FENG Bo, GAO Lin, JIANG Xiaohua, LIU Yuen Hang, RUDD A John, HOBBS Robin, QI Huayu, NG Tsz Kin, MAK Kayew Heather, LEUNG Kai Shun, LEE Tin-Lap
Journal nameStem Cells and Development
Year2019
Month10
Volume Number28
Issue Number20
PublisherMary Ann Liebert Inc.
Pages1365 - 1375
ISSN1547-3287
eISSN1557-8534
LanguagesEnglish-United Kingdom
Keywordsglaucoma, pluripotency, regenerative medicine, retinal ganglion cells, spermatogonial stem cells

Last updated on 2021-25-02 at 00:33