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

J Transl Med. 2013 Sep 27;11:236. doi: 10.1186/1479-5876-11-236.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Biomarkers / blood
  • Case-Control Studies
  • Cell Cycle
  • Cell Proliferation
  • Clone Cells
  • Colony-Forming Units Assay
  • Cytokines / blood
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fetal Blood / cytology
  • Heart Failure / blood
  • Heart Failure / pathology*
  • Humans
  • Infant, Newborn
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Middle Aged
  • Serum / metabolism
  • Signal Transduction
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases