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

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 th...

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Autores principales: Klose, Kristin, Roy, Rajika, Brodarac, Andreja, Kurtz, Andreas, Ode, Andrea, Kang, Kyung-Sun, Bieback, Karen, Choi, Yeong-Hoon, Stamm, Christof
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850697/
https://www.ncbi.nlm.nih.gov/pubmed/24074138
http://dx.doi.org/10.1186/1479-5876-11-236
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author Klose, Kristin
Roy, Rajika
Brodarac, Andreja
Kurtz, Andreas
Ode, Andrea
Kang, Kyung-Sun
Bieback, Karen
Choi, Yeong-Hoon
Stamm, Christof
author_facet Klose, Kristin
Roy, Rajika
Brodarac, Andreja
Kurtz, Andreas
Ode, Andrea
Kang, Kyung-Sun
Bieback, Karen
Choi, Yeong-Hoon
Stamm, Christof
author_sort Klose, Kristin
collection PubMed
description 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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spelling pubmed-38506972013-12-05 Impact of heart failure on the behavior of human neonatal stem cells in vitro Klose, Kristin Roy, Rajika Brodarac, Andreja Kurtz, Andreas Ode, Andrea Kang, Kyung-Sun Bieback, Karen Choi, Yeong-Hoon Stamm, Christof J Transl Med Research 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. BioMed Central 2013-09-27 /pmc/articles/PMC3850697/ /pubmed/24074138 http://dx.doi.org/10.1186/1479-5876-11-236 Text en Copyright © 2013 Klose et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Klose, Kristin
Roy, Rajika
Brodarac, Andreja
Kurtz, Andreas
Ode, Andrea
Kang, Kyung-Sun
Bieback, Karen
Choi, Yeong-Hoon
Stamm, Christof
Impact of heart failure on the behavior of human neonatal stem cells in vitro
title Impact of heart failure on the behavior of human neonatal stem cells in vitro
title_full Impact of heart failure on the behavior of human neonatal stem cells in vitro
title_fullStr Impact of heart failure on the behavior of human neonatal stem cells in vitro
title_full_unstemmed Impact of heart failure on the behavior of human neonatal stem cells in vitro
title_short Impact of heart failure on the behavior of human neonatal stem cells in vitro
title_sort impact of heart failure on the behavior of human neonatal stem cells in vitro
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850697/
https://www.ncbi.nlm.nih.gov/pubmed/24074138
http://dx.doi.org/10.1186/1479-5876-11-236
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