{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:34:06Z","timestamp":1787747646428,"version":"build-2784847793"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>\n                    Rett syndrome (RTT) is a severe X-linked dominant neurodevelopmental disorder caused by mutations in the methyl-CpG-binding protein 2 (\n                    <jats:italic>MECP2<\/jats:italic>\n                    ) gene;\n                    <jats:italic>MeCP2<\/jats:italic>\n                    regulates the expression of brain-derived neurotrophic factor (\n                    <jats:italic>BDNF<\/jats:italic>\n                    ) and increasing BDNF levels ameliorates RTT symptoms. However, the clinical application of BDNF is limited, because of its short half-life and low penetrance across the blood-brain barrier. In this study, we generated BDNF-secreting mesenchymal stem cells (MSCs) from the human umbilical cord cells, using CRISPR-Cas9. We studied the effects of BDNF-MSCs in\n                    <jats:italic>MECP2<\/jats:italic>\n                    knockout and\n                    <jats:italic>MECP2<\/jats:italic>\n                    -deficient mice. BDNF-MSCs upregulated the expression of BDNF, pAKT, and pERK1\/2 and downregulated that of pp38, both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In our\n                    <jats:italic>in vivo<\/jats:italic>\n                    experiments, BDNF-MSCs increased the body and brain weights in mice. BDNF-MSCs increased the neuronal cell numbers in the hippocampus, cortex, and striatum; in addition, they increased the number of synapses. BDNF-MSCs upregulated BDNF and the activity of BDNF downstream effectors, such as pAKT and pERK 1\/2; this upregulation was persistent. In conclusion, BDNF-MSCs generated using CRISPR-Cas9 could be a therapeutic strategy for treating RTT.\n                  <\/jats:p>","DOI":"10.3389\/fnins.2021.725398","type":"journal-article","created":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T20:53:46Z","timestamp":1633553626000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Brain-Derived Neurotrophic Factor Secreting Human Mesenchymal Stem Cells Improve Outcomes in Rett Syndrome Mouse Models"],"prefix":"10.3389","volume":"15","author":[{"given":"Hyo Jeong","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delger","family":"Bayarsaikhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaesuk","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Govigerel","family":"Bayarsaikhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonghee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"214","DOI":"10.4161\/epi.2.4.5212","article-title":"MeCP2 deficiency in the brain decreases BDNF levels by REST\/CoREST-mediated repression and increases TRKB production.","volume":"2","author":"Abuhatzira","year":"2007","journal-title":"Epigenetics"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.24966\/SRDT-2060\/100060","article-title":"AGE-RAGE System and its Application in Stem Cell Therapy.","volume":"7","author":"Bayarsaikhan","year":"2020","journal-title":"J. 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