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However, the majority of transplanted cells often die soon after transplantation, and those that survive initially continue to die in the subacute phase, diminishing the impact of transplantations. In this study, we genetically modified transplanted human neural stem cells (hNSCs), from 2 distant embryonic stem cell lines (H9 and RC17), to express 1 of 4 prosurvival factors \u2014 Hif1a, Akt1, Bcl-2, or Bcl-xl \u2014 and studied how these modifications improve short- and long-term survival of transplanted hNSCs. All genetic modifications dramatically increased survival of the transplanted hNSCs. Importantly, 3 out of 4 modifications also enhanced the exit of hNSCs from the cell cycle, thus avoiding aberrant growth of the transplants. Bcl-xl expression provided the strongest protection of transplanted cells, reducing both immediate and delayed cell death, and stimulated hNSC differentiation toward neuronal and oligodendroglial lineages. By designing hNSCs with drug-controlled expression of Bcl-xl, we demonstrated that short-term expression of a prosurvival factor can ensure the long-term survival of transplanted cells. Importantly, transplantation of Bcl-xl\u2013expressing hNSCs into mice suffering from stroke improved behavioral outcome and recovery of motor activity in mice.<\/jats:p>","DOI":"10.1172\/jci.insight.126268","type":"journal-article","created":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T12:00:46Z","timestamp":1580385646000},"source":"Crossref","is-referenced-by-count":40,"title":["Genetic modification increases the survival and the neuroregenerative properties of transplanted neural stem cells"],"prefix":"10.1172","volume":"5","author":[{"given":"Irina","family":"Korshunova","sequence":"first","affiliation":[{"name":"Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5788-7971","authenticated-orcid":true,"given":"Sina","family":"Rhein","sequence":"additional","affiliation":[{"name":"Institute for Experimental and Clinical Pharmacology and Toxicology, 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