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

Publication ,  Journal Article
Klose, K; Roy, R; Brodarac, A; Kurtz, A; Ode, A; Kang, K-S; Bieback, K; Choi, Y-H; Stamm, C
Published in: J Transl Med
September 27, 2013

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.

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Published In

J Transl Med

DOI

EISSN

1479-5876

Publication Date

September 27, 2013

Volume

11

Start / End Page

236

Location

England

Related Subject Headings

  • Young Adult
  • Signal Transduction
  • Serum
  • Middle Aged
  • Mesenchymal Stem Cells
  • JNK Mitogen-Activated Protein Kinases
  • Infant, Newborn
  • Immunology
  • Humans
  • Heart Failure
 

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Klose, K., Roy, R., Brodarac, A., Kurtz, A., Ode, A., Kang, K.-S., … Stamm, C. (2013). Impact of heart failure on the behavior of human neonatal stem cells in vitro. J Transl Med, 11, 236. https://doi.org/10.1186/1479-5876-11-236
Klose, Kristin, Rajika Roy, Andreja Brodarac, Andreas Kurtz, Andrea Ode, Kyung-Sun Kang, Karen Bieback, Yeong-Hoon Choi, and Christof Stamm. “Impact of heart failure on the behavior of human neonatal stem cells in vitro.J Transl Med 11 (September 27, 2013): 236. https://doi.org/10.1186/1479-5876-11-236.
Klose K, Roy R, Brodarac A, Kurtz A, Ode A, Kang K-S, et al. Impact of heart failure on the behavior of human neonatal stem cells in vitro. J Transl Med. 2013 Sep 27;11:236.
Klose, Kristin, et al. “Impact of heart failure on the behavior of human neonatal stem cells in vitro.J Transl Med, vol. 11, Sept. 2013, p. 236. Pubmed, doi:10.1186/1479-5876-11-236.
Klose K, Roy R, Brodarac A, Kurtz A, Ode A, Kang K-S, Bieback K, Choi Y-H, Stamm C. Impact of heart failure on the behavior of human neonatal stem cells in vitro. J Transl Med. 2013 Sep 27;11:236.
Journal cover image

Published In

J Transl Med

DOI

EISSN

1479-5876

Publication Date

September 27, 2013

Volume

11

Start / End Page

236

Location

England

Related Subject Headings

  • Young Adult
  • Signal Transduction
  • Serum
  • Middle Aged
  • Mesenchymal Stem Cells
  • JNK Mitogen-Activated Protein Kinases
  • Infant, Newborn
  • Immunology
  • Humans
  • Heart Failure