Cargando…

Extracellular Vesicles Derived From Adult and Fetal Bone Marrow Mesenchymal Stromal Cells Differentially Promote ex vivo Expansion of Hematopoietic Stem and Progenitor Cells

Recently, we and others have illustrated that extracellular vesicles (EVs) have the potential to support hematopoietic stem and progenitor cell (HSPC) expansion; however, the mechanism and processes responsible for the intercellular communication by EVs are still unknown. In the current study, we in...

Descripción completa

Detalles Bibliográficos
Autores principales: Ghebes, Corina A., Morhayim, Jess, Kleijer, Marion, Koroglu, Merve, Erkeland, Stefan J., Hoogenboezem, Remco, Bindels, Eric, van Alphen, Floris P. J., van den Biggelaar, Maartje, Nolte, Martijn A., van der Eerden, Bram C. J., Braakman, Eric, Voermans, Carlijn, van de Peppel, Jeroen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947881/
https://www.ncbi.nlm.nih.gov/pubmed/33718342
http://dx.doi.org/10.3389/fbioe.2021.640419
_version_ 1783663319470571520
author Ghebes, Corina A.
Morhayim, Jess
Kleijer, Marion
Koroglu, Merve
Erkeland, Stefan J.
Hoogenboezem, Remco
Bindels, Eric
van Alphen, Floris P. J.
van den Biggelaar, Maartje
Nolte, Martijn A.
van der Eerden, Bram C. J.
Braakman, Eric
Voermans, Carlijn
van de Peppel, Jeroen
author_facet Ghebes, Corina A.
Morhayim, Jess
Kleijer, Marion
Koroglu, Merve
Erkeland, Stefan J.
Hoogenboezem, Remco
Bindels, Eric
van Alphen, Floris P. J.
van den Biggelaar, Maartje
Nolte, Martijn A.
van der Eerden, Bram C. J.
Braakman, Eric
Voermans, Carlijn
van de Peppel, Jeroen
author_sort Ghebes, Corina A.
collection PubMed
description Recently, we and others have illustrated that extracellular vesicles (EVs) have the potential to support hematopoietic stem and progenitor cell (HSPC) expansion; however, the mechanism and processes responsible for the intercellular communication by EVs are still unknown. In the current study, we investigate whether primary human bone marrow derived mesenchymal stromal cells (BMSC) EVs isolated from two different origins, fetal (fEV) and adult (aEV) tissue, can increase the relative low number of HSPCs found in umbilical cord blood (UCB) and which EV-derived components are responsible for ex vivo HSPC expansion. Interestingly, aEVs and to a lesser extent fEVs, showed supportive ex vivo expansion capacity of UCB-HSPCs. Taking advantage of the two BMSC sources with different supportive effects, we analyzed the EV cargo and investigated how gene expression is modulated in HSPCs after incubation with aEVs and fEVs. Proteomics analyses of the protein cargo composition of the supportive aEV vs. the less-supportive fEV identified 90% of the Top100 exosome proteins present in the ExoCarta database. Gene Ontology (GO) analyses illustrated that the proteins overrepresented in aEVs were annotated to oxidation-reduction process, mitochondrial ATP synthesis coupled proton transport, or protein folding. In contrast, the proteins overrepresented in fEVs were annotated to extracellular matrix organization positive regulation of cell migration or transforming growth factor beta receptor (TGFBR) signaling pathway. Small RNA sequencing identified different molecular signatures between aEVs and fEVs. Interestingly, the microRNA cluster miR-99b/let-7e/miR-125a, previously identified to increase the number of HSPCs by targeting multiple pro-apoptotic genes, was highly and significantly enriched in aEVs. Although we identified significant differences in the supportive effects of aEVs and fEVs, RNAseq analyses of the 24 h treated HSPCs indicated that a limited set of genes was differentially regulated when compared to cells that were treated with cytokines only. Together, our study provides novel insights into the complex biological role of EVs and illustrates that aEVs and fEVs differentially support ex vivo expansion capacity of UCB-HSPCs. Together opening new means for the application of EVs in the discovery of therapeutics for more efficient ex vivo HSPC expansion.
format Online
Article
Text
id pubmed-7947881
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-79478812021-03-12 Extracellular Vesicles Derived From Adult and Fetal Bone Marrow Mesenchymal Stromal Cells Differentially Promote ex vivo Expansion of Hematopoietic Stem and Progenitor Cells Ghebes, Corina A. Morhayim, Jess Kleijer, Marion Koroglu, Merve Erkeland, Stefan J. Hoogenboezem, Remco Bindels, Eric van Alphen, Floris P. J. van den Biggelaar, Maartje Nolte, Martijn A. van der Eerden, Bram C. J. Braakman, Eric Voermans, Carlijn van de Peppel, Jeroen Front Bioeng Biotechnol Bioengineering and Biotechnology Recently, we and others have illustrated that extracellular vesicles (EVs) have the potential to support hematopoietic stem and progenitor cell (HSPC) expansion; however, the mechanism and processes responsible for the intercellular communication by EVs are still unknown. In the current study, we investigate whether primary human bone marrow derived mesenchymal stromal cells (BMSC) EVs isolated from two different origins, fetal (fEV) and adult (aEV) tissue, can increase the relative low number of HSPCs found in umbilical cord blood (UCB) and which EV-derived components are responsible for ex vivo HSPC expansion. Interestingly, aEVs and to a lesser extent fEVs, showed supportive ex vivo expansion capacity of UCB-HSPCs. Taking advantage of the two BMSC sources with different supportive effects, we analyzed the EV cargo and investigated how gene expression is modulated in HSPCs after incubation with aEVs and fEVs. Proteomics analyses of the protein cargo composition of the supportive aEV vs. the less-supportive fEV identified 90% of the Top100 exosome proteins present in the ExoCarta database. Gene Ontology (GO) analyses illustrated that the proteins overrepresented in aEVs were annotated to oxidation-reduction process, mitochondrial ATP synthesis coupled proton transport, or protein folding. In contrast, the proteins overrepresented in fEVs were annotated to extracellular matrix organization positive regulation of cell migration or transforming growth factor beta receptor (TGFBR) signaling pathway. Small RNA sequencing identified different molecular signatures between aEVs and fEVs. Interestingly, the microRNA cluster miR-99b/let-7e/miR-125a, previously identified to increase the number of HSPCs by targeting multiple pro-apoptotic genes, was highly and significantly enriched in aEVs. Although we identified significant differences in the supportive effects of aEVs and fEVs, RNAseq analyses of the 24 h treated HSPCs indicated that a limited set of genes was differentially regulated when compared to cells that were treated with cytokines only. Together, our study provides novel insights into the complex biological role of EVs and illustrates that aEVs and fEVs differentially support ex vivo expansion capacity of UCB-HSPCs. Together opening new means for the application of EVs in the discovery of therapeutics for more efficient ex vivo HSPC expansion. Frontiers Media S.A. 2021-02-25 /pmc/articles/PMC7947881/ /pubmed/33718342 http://dx.doi.org/10.3389/fbioe.2021.640419 Text en Copyright © 2021 Ghebes, Morhayim, Kleijer, Koroglu, Erkeland, Hoogenboezem, Bindels, van Alphen, van den Biggelaar, Nolte, van der Eerden, Braakman, Voermans and van de Peppel. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Ghebes, Corina A.
Morhayim, Jess
Kleijer, Marion
Koroglu, Merve
Erkeland, Stefan J.
Hoogenboezem, Remco
Bindels, Eric
van Alphen, Floris P. J.
van den Biggelaar, Maartje
Nolte, Martijn A.
van der Eerden, Bram C. J.
Braakman, Eric
Voermans, Carlijn
van de Peppel, Jeroen
Extracellular Vesicles Derived From Adult and Fetal Bone Marrow Mesenchymal Stromal Cells Differentially Promote ex vivo Expansion of Hematopoietic Stem and Progenitor Cells
title Extracellular Vesicles Derived From Adult and Fetal Bone Marrow Mesenchymal Stromal Cells Differentially Promote ex vivo Expansion of Hematopoietic Stem and Progenitor Cells
title_full Extracellular Vesicles Derived From Adult and Fetal Bone Marrow Mesenchymal Stromal Cells Differentially Promote ex vivo Expansion of Hematopoietic Stem and Progenitor Cells
title_fullStr Extracellular Vesicles Derived From Adult and Fetal Bone Marrow Mesenchymal Stromal Cells Differentially Promote ex vivo Expansion of Hematopoietic Stem and Progenitor Cells
title_full_unstemmed Extracellular Vesicles Derived From Adult and Fetal Bone Marrow Mesenchymal Stromal Cells Differentially Promote ex vivo Expansion of Hematopoietic Stem and Progenitor Cells
title_short Extracellular Vesicles Derived From Adult and Fetal Bone Marrow Mesenchymal Stromal Cells Differentially Promote ex vivo Expansion of Hematopoietic Stem and Progenitor Cells
title_sort extracellular vesicles derived from adult and fetal bone marrow mesenchymal stromal cells differentially promote ex vivo expansion of hematopoietic stem and progenitor cells
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947881/
https://www.ncbi.nlm.nih.gov/pubmed/33718342
http://dx.doi.org/10.3389/fbioe.2021.640419
work_keys_str_mv AT ghebescorinaa extracellularvesiclesderivedfromadultandfetalbonemarrowmesenchymalstromalcellsdifferentiallypromoteexvivoexpansionofhematopoieticstemandprogenitorcells
AT morhayimjess extracellularvesiclesderivedfromadultandfetalbonemarrowmesenchymalstromalcellsdifferentiallypromoteexvivoexpansionofhematopoieticstemandprogenitorcells
AT kleijermarion extracellularvesiclesderivedfromadultandfetalbonemarrowmesenchymalstromalcellsdifferentiallypromoteexvivoexpansionofhematopoieticstemandprogenitorcells
AT koroglumerve extracellularvesiclesderivedfromadultandfetalbonemarrowmesenchymalstromalcellsdifferentiallypromoteexvivoexpansionofhematopoieticstemandprogenitorcells
AT erkelandstefanj extracellularvesiclesderivedfromadultandfetalbonemarrowmesenchymalstromalcellsdifferentiallypromoteexvivoexpansionofhematopoieticstemandprogenitorcells
AT hoogenboezemremco extracellularvesiclesderivedfromadultandfetalbonemarrowmesenchymalstromalcellsdifferentiallypromoteexvivoexpansionofhematopoieticstemandprogenitorcells
AT bindelseric extracellularvesiclesderivedfromadultandfetalbonemarrowmesenchymalstromalcellsdifferentiallypromoteexvivoexpansionofhematopoieticstemandprogenitorcells
AT vanalphenflorispj extracellularvesiclesderivedfromadultandfetalbonemarrowmesenchymalstromalcellsdifferentiallypromoteexvivoexpansionofhematopoieticstemandprogenitorcells
AT vandenbiggelaarmaartje extracellularvesiclesderivedfromadultandfetalbonemarrowmesenchymalstromalcellsdifferentiallypromoteexvivoexpansionofhematopoieticstemandprogenitorcells
AT noltemartijna extracellularvesiclesderivedfromadultandfetalbonemarrowmesenchymalstromalcellsdifferentiallypromoteexvivoexpansionofhematopoieticstemandprogenitorcells
AT vandereerdenbramcj extracellularvesiclesderivedfromadultandfetalbonemarrowmesenchymalstromalcellsdifferentiallypromoteexvivoexpansionofhematopoieticstemandprogenitorcells
AT braakmaneric extracellularvesiclesderivedfromadultandfetalbonemarrowmesenchymalstromalcellsdifferentiallypromoteexvivoexpansionofhematopoieticstemandprogenitorcells
AT voermanscarlijn extracellularvesiclesderivedfromadultandfetalbonemarrowmesenchymalstromalcellsdifferentiallypromoteexvivoexpansionofhematopoieticstemandprogenitorcells
AT vandepeppeljeroen extracellularvesiclesderivedfromadultandfetalbonemarrowmesenchymalstromalcellsdifferentiallypromoteexvivoexpansionofhematopoieticstemandprogenitorcells