Transplantation of Retinal Ganglion Cells Derived from Male Germline Stem Cell as a Potential Treatment to Glaucoma

• Published in: Stem cells and development Vol. 28; no. 20; p. 1365
• Main Authors: Suen, Hoi Ching, Qian, Yan, Liao, Jinyue, Luk, Chun Shui, Lee, Wing Tung, Ng, Judy Kin Wing, Chan, Thomas Ting Hei, Hou, Hei Wan, Li, Ingrid, Li, Kit, Chan, Wai-Yee, Feng, Bo, Gao, Lin, Jiang, Xiaohua, Liu, Yuen Hang, Rudd, John A, Hobbs, Robin, Qi, Huayu, Ng, Tsz Kin, Mak, Heather Kayew, Leung, Kai Shun, Lee, Tin-Lap
• Format: Journal Article
• Language: English
• Published: United States 15.10.2019
• Subjects: retinal ganglion cells; pluripotency; spermatogonial stem cells; glaucoma; regenerative medicine
• ISSN: 1557-8534
• DOI: 10.1089/scd.2019.0060

Glaucoma 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 and functioned as 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.