{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:34:19Z","timestamp":1790645659053,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T00:00:00Z","timestamp":1596153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DLFH Aktion f\u00fcr Krebskranke Kinder Mannheim","award":["n.a."],"award-info":[{"award-number":["n.a."]}]},{"name":"mcon goes golf","award":["n.a."],"award-info":[{"award-number":["n.a."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Central nervous System (CNS) disease in pediatric acute lymphoblastic leukemia (ALL) is a major concern, but still, cellular mechanisms of CNS infiltration are elusive. The choroid plexus (CP) is a potential entry site, and, to some extent, invasion resembles CNS homing of lymphocytes during healthy state. Given exosomes may precondition target tissue, the present work aims to investigate if leukemia-derived exosomes contribute to a permissive phenotype of the blood-cerebrospinal fluid barrier (BCSFB). Leukemia-derived exosomes were isolated by ultracentrifugation from the cell lines SD-1, Nalm-6, and P12-Ichikawa (P12). Adhesion and uptake to CP epithelial cells and the significance on subsequent ALL transmigration across the barrier was studied in a human BCSFB in vitro model based on the HiBCPP cell line. The various cell lines markedly differed regarding exosome uptake to HiBCPP and biological significance. SD-1-derived exosomes associated to target cells unspecifically without detectable cellular effects. Whereas Nalm-6 and P12-derived exosomes incorporated by dynamin-dependent endocytosis, uptake in the latter could be diminished by integrin blocking. In addition, only P12-derived exosomes led to facilitated transmigration of the parental leukemia cells. In conclusion, we provide evidence that, to a varying extent, leukemia-derived exosomes may facilitate CNS invasion of ALL across the BCSFB without destruction of the barrier integrity.<\/jats:p>","DOI":"10.3390\/ijms21155491","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T06:16:47Z","timestamp":1596435407000},"page":"5491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Impact of Small Extracellular Vesicles on Lymphoblast Trafficking across the Blood-Cerebrospinal Fluid Barrier In Vitro"],"prefix":"10.3390","volume":"21","author":[{"given":"Ulrike","family":"Erb","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University Medical Center Mannheim, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Hikel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Mannheim, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Mannheim, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Regenerative Medicine, Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, 1\u20131\u20131 Tennodai, Tsukuba, Ibaraki 305\u20138575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Worst","sequence":"additional","affiliation":[{"name":"Department of Urology and Urosurgery, University Medical Center Mannheim, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Nitschke","sequence":"additional","affiliation":[{"name":"Department of Urology and Urosurgery, University Medical Center Mannheim, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Nuhn","sequence":"additional","affiliation":[{"name":"Department of Urology and Urosurgery, University Medical Center Mannheim, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Porubsky","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, 55101 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christel","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics and Biomathematics, University Medical Center Mannheim, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst","family":"Schroten","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Mannheim, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2150-8199","authenticated-orcid":false,"given":"R\u00fcdiger","family":"Adam","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Mannheim, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9961-4752","authenticated-orcid":false,"given":"Michael","family":"Karremann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Mannheim, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1056\/NEJMra1400972","article-title":"Acute lymphoblastic leukemia in children","volume":"373","author":"Hunger","year":"2015","journal-title":"N. 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