{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:40:14Z","timestamp":1784310014318,"version":"3.55.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":1519,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["HA 7512\/2-1"],"award-info":[{"award-number":["HA 7512\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Left ventricular (LV) diastolic dysfunction is among others attributed to cardiomyocyte stiffness. Mesenchymal stromal cells (MSC) have cardiac-protective properties. We explored whether intravenous (i.v.) application of PLacenta-eXpanded (PLX) MSC-like cells (PLX) improves LV diastolic relaxation in streptozotocin (STZ)-induced diabetic mice and investigated underlying mechanisms. Diabetes mellitus was induced by STZ application (50 mg\/kg body weight) during five subsequent days. One week after the first STZ injection, PLX or saline were i.v. applied. Two weeks later, mice were hemodynamically characterized and sacrificed. At this early stage of diabetic cardiomyopathy with low-grade inflammation and no cardiac fibrosis, PLX reduced LV vascular cell adhesion molecule-1, transforming growth factor-\u03b21, and interferon-\u03b3 mRNA expression, induced the percentage of circulating regulatory T cells, and decreased the splenic pro-fibrotic potential in STZ mice. STZ\u2009+\u2009PLX mice exhibited higher LV vascular endothelial growth factor mRNA expression and arteriole density versus STZ mice. In vitro, hyperglycemic PLX conditioned medium restored the hyperglycemia-impaired tube formation and adhesion capacity of human umbelical vein endothelial cells (HUVEC) via increasing nitric oxide (NO) bioavailability. PLX further induced the diabetes-downregulated activity of the NO downstream protein kinase G, as well as of protein kinase A, in STZ mice, which was associated with a raise in phosphorylation of the titin isoforms N2BA and N2B. Concomitantly, the passive force was lower in single isolated cardiomyocytes from STZ\u2009+\u2009PLX versus from STZ mice, which led to an improvement of LV diastolic relaxation. We conclude that i.v. PLX injection improves diabetes mellitus-associated diastolic performance via decreasing cardiomyocyte stiffness.<\/jats:p>","DOI":"10.1002\/sctm.17-0130","type":"journal-article","created":{"date-parts":[[2017,10,10]],"date-time":"2017-10-10T18:36:18Z","timestamp":1507660578000},"page":"2135-2145","source":"Crossref","is-referenced-by-count":29,"title":["Placenta-Derived Adherent Stromal Cells Improve Diabetes Mellitus-Associated Left Ventricular Diastolic Performance"],"prefix":"10.1093","volume":"6","author":[{"given":"Sophie","family":"Van Linthout","sequence":"first","affiliation":[{"name":"a Berlin-Brandenburg Center for Regenerative Therapies, Campus Virchow Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Germany"},{"name":"b Department of Cardiology, Charit\u00e9 \u2013 University Medicine Berlin, Campus Virchow, Berlin, Germany"},{"name":"c DZHK (German Center for Cardiovascular Research) partner site Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazha","family":"Hamdani","sequence":"additional","affiliation":[{"name":"d Department of Cardiovascular Physiology, Ruhr University Bochum, Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kapka","family":"Miteva","sequence":"additional","affiliation":[{"name":"a Berlin-Brandenburg Center for Regenerative Therapies, Campus Virchow Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Germany"},{"name":"b Department of Cardiology, Charit\u00e9 \u2013 University Medicine Berlin, Campus Virchow, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Koschel","sequence":"additional","affiliation":[{"name":"a Berlin-Brandenburg Center for Regenerative Therapies, Campus Virchow Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"a Berlin-Brandenburg Center for Regenerative Therapies, Campus Virchow Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Germany"},{"name":"c DZHK (German Center for Cardiovascular Research) partner site Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Pinzur","sequence":"additional","affiliation":[{"name":"e Pluristem Therapeutics Inc, Haifa, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zami","family":"Aberman","sequence":"additional","affiliation":[{"name":"e Pluristem Therapeutics Inc, Haifa, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Pappritz","sequence":"additional","affiliation":[{"name":"a Berlin-Brandenburg Center for Regenerative Therapies, Campus Virchow Charit\u00e9 \u2013 Universit\u00e4tsmedizin 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