{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:20:04Z","timestamp":1783635604693,"version":"3.55.0"},"reference-count":33,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,20]],"date-time":"2021-11-20T00:00:00Z","timestamp":1637366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &amp; Welfare, Republic of Korea","award":["HI16C1559"],"award-info":[{"award-number":["HI16C1559"]}]},{"name":"the National Research Foundation of Korea (NRF), funded by the Korean government","award":["2021R1A2C201052311"],"award-info":[{"award-number":["2021R1A2C201052311"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human pluripotent stem cell-derived neural progenitor cells (NPCs) have the potential to recover from nerve injury. We previously reported that human placenta-derived mesenchymal stem cells (PSCs) have neuroprotective effects. To evaluate the potential benefit of NPCs, we compared them to PSCs using R28 cells under hypoxic conditions and a rat model of optic nerve injury. NPCs and PSCs (2 \u00d7 106 cells) were injected into the subtenon space. After 1, 2, and 4 weeks, we examined changes in target proteins in the retina and optic nerve. NPCs significantly induced vascular endothelial growth factor (Vegf) compared to age-matched shams and PSC groups at 2 weeks; they also induced neurofilaments in the retina compared to the sham group at 4 weeks. In addition, the expression of brain-derived neurotrophic factor (Bdnf) was high in the retina in the NPC group at 2 weeks, while expression in the optic nerve was high in both the NPC and PSC groups. The low expression of ionized calcium-binding adapter molecule 1 (Iba1) in the retina had recovered at 2 weeks after NPC injection and at 4 weeks after PSC injection. The expression of the inflammatory protein NLR family, pyrin domain containing 3 (Nlrp3) was significantly reduced at 1 week, and that of tumor necrosis factor-\u03b1 (Tnf-\u03b1) in the optic nerves of the NPC group was lower at 2 weeks. Regarding retinal ganglion cells, the expressions of Brn3a and Tuj1 in the retina were enhanced in the NPC group compared to sham controls at 4 weeks. NPC injections increased Gap43 expression from 2 weeks and reduced Iba1 expression in the optic nerves during the recovery period. In addition, R28 cells exposed to hypoxic conditions showed increased cell survival when cocultured with NPCs compared to PSCs. Both Wnt\/\u03b2-catenin signaling and increased Nf-\u0138b could contribute to the rescue of damaged retinal ganglion cells via upregulation of neuroprotective factors, microglial engagement, and anti-inflammatory regulation by NPCs. This study suggests that NPCs could be useful for the cellular treatment of various optic neuropathies, together with cell therapy using mesenchymal stem cells.<\/jats:p>","DOI":"10.3390\/ijms222212529","type":"journal-article","created":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T20:58:21Z","timestamp":1637528301000},"page":"12529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Human Pluripotent Stem Cell-Derived Neural Progenitor Cells Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model"],"prefix":"10.3390","volume":"22","author":[{"given":"Mira","family":"Park","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Mun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA University, Seongnam 13488, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Ah","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Youn","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA University, Seongnam 13488, Gyeonggi-do, Korea"},{"name":"Department of Microbiology, School of Medicine, CHA University, Seongnam 13488, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0121-3000","authenticated-orcid":false,"given":"Helen","family":"Lew","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3362","DOI":"10.1007\/s12035-020-01965-8","article-title":"Hypoxia-Preconditioned Placenta-Derived Mesenchymal Stem Cells Rescue Optic Nerve Axons via Differential Roles of Vascular Endothelial Growth Factor in an Optic Nerve Compression Animal Model","volume":"57","author":"Kwon","year":"2020","journal-title":"Mol. 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