{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:03:22Z","timestamp":1770897802428,"version":"3.50.1"},"reference-count":73,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T00:00:00Z","timestamp":1623456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["241879"],"award-info":[{"award-number":["241879"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["643809"],"award-info":[{"award-number":["643809"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sanit\u00e4tsakademie der Bundeswehr","award":["E\/U2AD\/ID018\/IF557"],"award-info":[{"award-number":["E\/U2AD\/ID018\/IF557"]}]},{"name":"Bundesministerium f\u00fcr Bildung und Forschung and Federal States of Germany Grant \u201cInnovative Hochschule\u201d","award":["FKZ 3IHS024D"],"award-info":[{"award-number":["FKZ 3IHS024D"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human multipotent mesenchymal stromal cells (hMSCs) are currently developed as cell therapeutics for different applications, including regenerative medicine, immune modulation, and cancer treatment. The biological properties of hMSCs can be further modulated by genetic engineering. Viral vectors based on human adenovirus type 5 (HAdV-5) belong to the most frequently used vector types for genetic modification of human cells in vitro and in vivo. However, due to a lack of the primary attachment receptor coxsackievirus and adenovirus receptor (CAR) in hMSCs, HAdV-5 vectors are currently not suitable for transduction of this cell type without capsid modification. Here we present several transduction enhancers that strongly enhance HAdV-5-mediated gene transfer into both bone marrow- and adipose tissue-derived hMSCs. Polybrene, poly-l-lysine, human lactoferrin, human blood coagulation factor X, spermine, and spermidine enabled high eGFP expression levels in hMSCs. Importantly, hMSCs treated with enhancers were not affected in their migration behavior, which is a key requisite for many therapeutic applications. Exemplary, strongly increased expression of tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6) (a secreted model therapeutic protein) was achieved by enhancer-facilitated HAdV-5 transduction. Thus, enhancer-mediated HAdV-5 vector transduction is a valuable method for the engineering of hMSCs, which can be further exploited for the development of innovative hMSC therapeutics.<\/jats:p>","DOI":"10.3390\/v13061136","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T22:26:01Z","timestamp":1623709561000},"page":"1136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Transduction Enhancers Enable Efficient Human Adenovirus Type 5-Mediated Gene Transfer into Human Multipotent Mesenchymal Stromal Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2528-9547","authenticated-orcid":false,"given":"Robin","family":"Nilson","sequence":"first","affiliation":[{"name":"Department of Gene Therapy, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia","family":"L\u00fcbbers","sequence":"additional","affiliation":[{"name":"Department of Gene Therapy, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linus","family":"Wei\u00df","sequence":"additional","affiliation":[{"name":"Department of Gene Therapy, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1237-7417","authenticated-orcid":false,"given":"Karmveer","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Scharffetter-Kochanek","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4265-0442","authenticated-orcid":false,"given":"Markus","family":"Rojewski","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine, University Medical Center Ulm, 89081 Ulm, Germany"},{"name":"Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Donation Service, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hubert","family":"Schrezenmeier","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine, University Medical Center Ulm, 89081 Ulm, Germany"},{"name":"Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Donation Service, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip Helge","family":"Zeplin","sequence":"additional","affiliation":[{"name":"Schlosspark Klinik Ludwigsburg, Privatklinik f\u00fcr Plastische und \u00c4sthetische Chirurgie, 71638 Ludwigsburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Funk","sequence":"additional","affiliation":[{"name":"Sch\u00f6nheitsklinik Dr. Funk, 81739 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4092-4131","authenticated-orcid":false,"given":"Lea","family":"Krutzke","sequence":"additional","affiliation":[{"name":"Department of Gene Therapy, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Kochanek","sequence":"additional","affiliation":[{"name":"Department of Gene Therapy, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6779-0412","authenticated-orcid":false,"given":"Astrid","family":"Kritzinger","sequence":"additional","affiliation":[{"name":"Department of Gene Therapy, University Medical Center Ulm, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal Criteria for Defining Multipotent Mesenchymal Stromal Cells. 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