dc.contributor.author
Bader, Andreas Matthäus
dc.contributor.author
Klose, Kristin
dc.contributor.author
Bieback, Karen
dc.contributor.author
Korinth, Dirk
dc.contributor.author
Schneider, Maria
dc.contributor.author
Seifert, Martina
dc.contributor.author
Choi, Yeong-Hoon
dc.contributor.author
Kurtz, Andreas
dc.contributor.author
Falk, Volkmar
dc.contributor.author
Stamm, Christof
dc.date.accessioned
2018-06-08T03:25:54Z
dc.date.available
2015-10-30T11:36:59.913Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/15169
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-19357
dc.description.abstract
Hypoxic preconditioning was shown to improve the therapeutic efficacy of bone
marrow-derived multipotent mesenchymal stromal cells (MSCs) upon
transplantation in ischemic tissue. Given the interest in clinical
applications of umbilical cord blood-derived MSCs, we developed a specific
hypoxic preconditioning protocol and investigated its anti-apoptotic and pro-
angiogenic effects on cord blood MSCs undergoing simulated ischemia in vitro
by subjecting them to hypoxia and nutrient deprivation with or without
preceding hypoxic preconditioning. Cell number, metabolic activity, surface
marker expression, chromosomal stability, apoptosis (caspases-3/7 activity)
and necrosis were determined, and phosphorylation, mRNA expression and protein
secretion of selected apoptosis and angiogenesis-regulating factors were
quantified. Then, human umbilical vein endothelial cells (HUVEC) were
subjected to simulated ischemia in co-culture with hypoxically preconditioned
or naïve cord blood MSCs, and HUVEC proliferation was measured. Migration,
proliferation and nitric oxide production of HUVECs were determined in
presence of cord blood MSC-conditioned medium. Cord blood MSCs proved least
sensitive to simulated ischemia when they were preconditioned for 24 h, while
their basic behavior, immunophenotype and karyotype in culture remained
unchanged. Here, “post-ischemic” cell number and metabolic activity were
enhanced and caspase-3/7 activity and lactate dehydrogenase release were
reduced as compared to non-preconditioned cells. Phosphorylation of AKT and
BAD, mRNA expression of BCL-XL, BAG1 and VEGF, and VEGF protein secretion were
higher in preconditioned cells. Hypoxically preconditioned cord blood MSCs
enhanced HUVEC proliferation and migration, while nitric oxide production
remained unchanged. We conclude that hypoxic preconditioning protects cord
blood MSCs by activation of anti-apoptotic signaling mechanisms and enhances
their angiogenic potential. Hence, hypoxic preconditioning might be a
translationally relevant strategy to increase the tolerance of cord blood MSCs
to ischemia and improve their therapeutic efficacy in clinical applications.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Hypoxic Preconditioning Increases Survival and Pro-Angiogenic Capacity of
Human Cord Blood Mesenchymal Stromal Cells In Vitro
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
PLoS ONE. - 10 (2015), 9, Artikel Nr. e0138477
dcterms.bibliographicCitation.doi
10.1371/journal.pone.0138477
dcterms.bibliographicCitation.url
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138477
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000023374
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000005596
dcterms.accessRights.openaire
open access