Impact of heart failure on the behavior of human neonatal stem cells in vitro

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Heart failure temporarily inhibits clonality and proliferation of “healthy” juvenile MSC <jats:italic>in vitro</jats:italic>. Further studies should address the <jats:italic>in vivo</jats:italic> and clinical relevance of this finding.</jats:p> </jats:sec>

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Published Version (Please cite this version)

10.1186/1479-5876-11-236

Publication Info

Klose, Kristin, Rajika Roy, Andreja Brodarac, Andreas Kurtz, Andrea Ode, Kyung-Sun Kang, Karen Bieback, Yeong-Hoon Choi, et al. (2013). Impact of heart failure on the behavior of human neonatal stem cells in vitro. Journal of Translational Medicine, 11(1). 10.1186/1479-5876-11-236 Retrieved from https://hdl.handle.net/10161/28947.

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