Abstract

Background: Clinical cardiac cell therapy using autologous somatic stem cells is restricted by age and disease-associated impairment of stem cell function. Juvenile cells possibly represent a more potent alternative, but the impact of patient-related variables on such cell products is unknown. We therefore evaluated the behavior of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum from patients with advanced heart failure (HF).Methods: Human serum was obtained from patients with severe HF (n = 21) and from healthy volunteers (n = 12). To confirm the systemic quality of HF in the sera, TNF-α and IL-6 were quantified. CB-MSC from healthy neonates were cultivated for up to 14 days in medium supplemented with 10% protein-normalized human HF or control serum or fetal calf serum (FCS).Results: All HF sera contained increased cytokine concentrations (IL-6, TNF-α). When exposed to HF serum, CB-MSC maintained basic MSC properties as confirmed by immunophenotyping and differentiation assays, but clonogenic cells were reduced in number and gave rise to substantially smaller colonies in the CFU-F assay. Cell cycle analysis pointed towards G1 arrest. CB-MSC metabolic activity and proliferation were significantly impaired for up to 3 days as measured by MTS turnover, BrdU incorporation and DAPI + nuclei counting. On day 5, however, CB-MSC growth kinetics approached control serum levels, though protein expression of cell cycle inhibitors (p21, p27), and apoptosis marker Caspase 3 remained elevated. Signal transduction included the stress and cytokine-induced JNK and ERK1/2 MAP kinase pathways.Conclusions: Heart failure temporarily inhibits clonality and proliferation of " healthy" juvenile MSC in vitro. Further studies should address the in vivo and clinical relevance of this finding. © 2013 Klose et al.; licensee BioMed Central Ltd.

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APA

K., K., R., R., A., B., A., K., A., O., K.-S., K., … C., S. (2013). Impact of heart failure on the behavior of human neonatal stem cells in vitro. Journal of Translational Medicine, 11(1), 236. https://doi.org/10.1186/1479-5876-11-236 LK  - http://WT3CF4ET2L.search.serialssolutions.com?sid=EMBASE&issn=14795876&id=doi:10.1186%2F1479-5876-11-236&atitle=Impact+of+heart+failure+on+the+behavior+of+human+neonatal+stem+cells+in+vitro&stitle=J.+Transl.+Med.&title=Journal+of+Translational+Medicine&volume=11&issue=1&spage=&epage=&aulast=Klose&aufirst=Kristin&auinit=K.&aufull=Klose+K.&coden=&isbn=&pages=-&date=2013&auinit1=K&auinitm=

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