{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T09:59:05Z","timestamp":1783763945153,"version":"3.55.0"},"reference-count":77,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T00:00:00Z","timestamp":1589155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korean Health Technology R&amp;D Project","award":["HI16C1089"],"award-info":[{"award-number":["HI16C1089"]}]},{"name":"the Bio &amp; Medical Technology Development Program of the National Research Foundation","award":["NRF-2019M3A9H1032791"],"award-info":[{"award-number":["NRF-2019M3A9H1032791"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neural progenitor cells (NPCs) therapy offers great promise in hypoxic-ischemic (HI) brain injury. However, the poor survival of implanted NPCs in the HI host environment limits their therapeutic effects. Tumor necrosis factor-alpha (TNF-\u03b1) is a pleiotropic cytokine that is induced in response to a variety of pathological processes including inflammation and immunity. On the other hand, TNF-\u03b1 has protective effects on cell apoptosis and death and affects the differentiation, proliferation, and survival of neural stem\/progenitor cells in the brain. The present study investigated whether TNF-\u03b1 pretreatment on human NPCs (hNPCs) enhances the effectiveness of cell transplantation therapy under ischemic brain. Fetal brain tissue-derived hNPCs were pretreated with TNF-\u03b1 before being used in vitro experiments or transplantation. TNF-\u03b1 significantly increased expression of cIAP2, and the use of short hairpin RNA-mediated knockdown of cIAP2 demonstrated that cIAP2 protected hNPCs against HI-induced cytotoxicity. In addition, pretreatment of hNPCs with TNF-\u03b1 mediated neuroprotection by altering microglia polarization via increased expression of CX3CL1 and by enhancing expression of neurotrophic factors. Furthermore, transplantation of TNF-\u03b1-treated hNPCs reduced infarct volume and improved neurological functions in comparison with non-pretreated hNPCs or vehicle. These findings show that TNF-\u03b1 pretreatment, which protects hNPCs from HI-injured brain-induced apoptosis and increases neuroprotection, is a simple and safe approach to improve the survival of transplanted hNPCs and the therapeutic efficacy of hNPCs in HI brain injury.<\/jats:p>","DOI":"10.3390\/cells9051195","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T12:26:30Z","timestamp":1589199990000},"page":"1195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["TNF-\u03b1 Pretreatment Improves the Survival and Function of Transplanted Human Neural Progenitor Cells Following Hypoxic-Ischemic Brain Injury"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0380-1677","authenticated-orcid":false,"given":"Miri","family":"Kim","sequence":"first","affiliation":[{"name":"Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwangsoo","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Severance Children\u2019s Hospital, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younhee","family":"Ko","sequence":"additional","affiliation":[{"name":"Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin 17035, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il-Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyujin","family":"Hwang","sequence":"additional","affiliation":[{"name":"Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hyung","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4376-8541","authenticated-orcid":false,"given":"Jeong Eun","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Severance Children\u2019s Hospital, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kook In","family":"Park","sequence":"additional","affiliation":[{"name":"Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Department of Pediatrics, Severance Children\u2019s Hospital, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1002\/ana.23647","article-title":"Neonatal encephalopathy: An inadequate term for hypoxic-ischemic encephalopathy","volume":"72","author":"Volpe","year":"2012","journal-title":"Ann. 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