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MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells

Hematopoietic regeneration after high dose chemotherapy necessitates activation of the stem cell pool. There is evidence that serum taken after chemotherapy comprises factors stimulating proliferation and self-renewal of CD34(+) hematopoietic stem and progenitor cells (HSPCs) – however, the nature o...

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Autores principales: Walenda, Thomas, Diener, Yvonne, Jost, Edgar, Morin-Kensicki, Elizabeth, Goecke, Tamme W., Bosio, Andreas, Rath, Björn, Brümmendorf, Tim H., Bissels, Ute, Wagner, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449031/
https://www.ncbi.nlm.nih.gov/pubmed/26024523
http://dx.doi.org/10.1371/journal.pone.0128231
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author Walenda, Thomas
Diener, Yvonne
Jost, Edgar
Morin-Kensicki, Elizabeth
Goecke, Tamme W.
Bosio, Andreas
Rath, Björn
Brümmendorf, Tim H.
Bissels, Ute
Wagner, Wolfgang
author_facet Walenda, Thomas
Diener, Yvonne
Jost, Edgar
Morin-Kensicki, Elizabeth
Goecke, Tamme W.
Bosio, Andreas
Rath, Björn
Brümmendorf, Tim H.
Bissels, Ute
Wagner, Wolfgang
author_sort Walenda, Thomas
collection PubMed
description Hematopoietic regeneration after high dose chemotherapy necessitates activation of the stem cell pool. There is evidence that serum taken after chemotherapy comprises factors stimulating proliferation and self-renewal of CD34(+) hematopoietic stem and progenitor cells (HSPCs) – however, the nature of these feedback signals is yet unclear. Here, we addressed the question if specific microRNAs (miRNAs) or metabolites are affected after high dose chemotherapy. Serum taken from the same patients before and after chemotherapy was supplemented for in vitro cultivation of HSPCs. Serum taken after chemotherapy significantly enhanced HSPC proliferation, better maintained a CD34(+) immunophenotype, and stimulated colony forming units. Microarray analysis revealed that 23 miRNAs changed in serum after chemotherapy – particularly, miRNA-320c and miRNA-1275 were down-regulated whereas miRNA-3663-3p was up-regulated. miRNA-320c was exemplarily inhibited by an antagomiR, which seemed to increase proliferation. Metabolomic profiling demonstrated that 44 metabolites were less abundant, whereas three (including 2-hydroxybutyrate and taurocholenate sulphate) increased in serum upon chemotherapy. Nine of these metabolites were subsequently tested for effects on HSPCs in vitro, but none of them exerted a clear concentration dependent effect on proliferation, immunophenotype and colony forming unit formation. Taken together, serum profiles of miRNAs and metabolites changed after chemotherapy. Rather than individually, these factors may act in concert to recruit HSPCs into action for hematopoietic regeneration.
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spelling pubmed-44490312015-06-09 MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells Walenda, Thomas Diener, Yvonne Jost, Edgar Morin-Kensicki, Elizabeth Goecke, Tamme W. Bosio, Andreas Rath, Björn Brümmendorf, Tim H. Bissels, Ute Wagner, Wolfgang PLoS One Research Article Hematopoietic regeneration after high dose chemotherapy necessitates activation of the stem cell pool. There is evidence that serum taken after chemotherapy comprises factors stimulating proliferation and self-renewal of CD34(+) hematopoietic stem and progenitor cells (HSPCs) – however, the nature of these feedback signals is yet unclear. Here, we addressed the question if specific microRNAs (miRNAs) or metabolites are affected after high dose chemotherapy. Serum taken from the same patients before and after chemotherapy was supplemented for in vitro cultivation of HSPCs. Serum taken after chemotherapy significantly enhanced HSPC proliferation, better maintained a CD34(+) immunophenotype, and stimulated colony forming units. Microarray analysis revealed that 23 miRNAs changed in serum after chemotherapy – particularly, miRNA-320c and miRNA-1275 were down-regulated whereas miRNA-3663-3p was up-regulated. miRNA-320c was exemplarily inhibited by an antagomiR, which seemed to increase proliferation. Metabolomic profiling demonstrated that 44 metabolites were less abundant, whereas three (including 2-hydroxybutyrate and taurocholenate sulphate) increased in serum upon chemotherapy. Nine of these metabolites were subsequently tested for effects on HSPCs in vitro, but none of them exerted a clear concentration dependent effect on proliferation, immunophenotype and colony forming unit formation. Taken together, serum profiles of miRNAs and metabolites changed after chemotherapy. Rather than individually, these factors may act in concert to recruit HSPCs into action for hematopoietic regeneration. Public Library of Science 2015-05-29 /pmc/articles/PMC4449031/ /pubmed/26024523 http://dx.doi.org/10.1371/journal.pone.0128231 Text en © 2015 Walenda et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Walenda, Thomas
Diener, Yvonne
Jost, Edgar
Morin-Kensicki, Elizabeth
Goecke, Tamme W.
Bosio, Andreas
Rath, Björn
Brümmendorf, Tim H.
Bissels, Ute
Wagner, Wolfgang
MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells
title MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells
title_full MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells
title_fullStr MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells
title_full_unstemmed MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells
title_short MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells
title_sort micrornas and metabolites in serum change after chemotherapy: impact on hematopoietic stem and progenitor cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449031/
https://www.ncbi.nlm.nih.gov/pubmed/26024523
http://dx.doi.org/10.1371/journal.pone.0128231
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