Universität zu Köln

Klose, Kristin, Roy, Rajika, Brodarac, Andreja, Kurtz, Andreas ORCID: 0000-0003-3301-6546, Ode, Andrea, Kang, Kyung-Sun, Bieback, Karen, Choi, Yeong-Hoon and Stamm, Christof (2013). Impact of heart failure on the behavior of human neonatal stem cells in vitro. J. Transl. Med., 11. LONDON: BIOMED CENTRAL LTD. ISSN 1479-5876

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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-alpha 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-alpha). 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klose, Kristin UNSPECIFIED UNSPECIFIED UNSPECIFIED Roy, Rajika UNSPECIFIED UNSPECIFIED UNSPECIFIED Brodarac, Andreja UNSPECIFIED UNSPECIFIED UNSPECIFIED Kurtz, Andreas UNSPECIFIED orcid.org/0000-0003-3301-6546 UNSPECIFIED Ode, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Kang, Kyung-Sun UNSPECIFIED UNSPECIFIED UNSPECIFIED Bieback, Karen UNSPECIFIED UNSPECIFIED UNSPECIFIED Choi, Yeong-Hoon UNSPECIFIED UNSPECIFIED UNSPECIFIED Stamm, Christof UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-475679
DOI:	10.1186/1479-5876-11-236
Journal or Publication Title:	J. Transl. Med.
Volume:	11
Date:	2013
Publisher:	BIOMED CENTRAL LTD
Place of Publication:	LONDON
ISSN:	1479-5876
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CORD BLOOD; THERAPY; DIFFERENTIATION; CAPACITY; DISEASE; DEATH; SERUM Multiple languages Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47567