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

被引:11
|
作者
Ghebes, Corina A. [1 ]
Morhayim, Jess [2 ]
Kleijer, Marion [1 ]
Koroglu, Merve [1 ]
Erkeland, Stefan J. [3 ]
Hoogenboezem, Remco [2 ]
Bindels, Eric [2 ]
van Alphen, Floris P. J. [4 ]
van den Biggelaar, Maartje [4 ]
Nolte, Martijn A. [1 ,4 ]
van der Eerden, Bram C. J. [5 ]
Braakman, Eric [2 ]
Voermans, Carlijn [1 ]
van de Peppel, Jeroen [5 ]
机构
[1] Sanquin Res, Dept Hematopoiesrs, Amsterdam, Netherlands
[2] Erasmus MC, Dept Hematol, Univ Med Ctr, Rotterdam, Netherlands
[3] Erasmus MC, Dept Immunol, Univ Med Ctr, Rotterdam, Netherlands
[4] Sanquin Res, Dept Mol Hematol, Amsterdam, Netherlands
[5] Erasmus MC, Dept Internal Med, Univ Med Ctr, Rotterdam, Netherlands
关键词
extracellular vesicles; BMSCs; HSPC expansion; transplantation; hematopoietic niche; intercellular communication; EV cargo;
D O I
10.3389/fbioe.2021.640419
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页数:14
相关论文
共 50 条
  • [11] Mesenchymal stem/stromal cells from human pluripotent stem cell-derived brain organoid enhance the ex vivo expansion and maintenance of hematopoietic stem/progenitor cells
    Ya Zhou
    Xinping Cai
    Xiuxiu Zhang
    Yong Dong
    Xu Pan
    Mowen Lai
    Yimeng Zhang
    Yijin Chen
    Xiaohong Li
    Xia Li
    Jiaxin Liu
    Yonggang Zhang
    Feng Ma
    Stem Cell Research & Therapy, 15
  • [12] Extracellular vesicles from bone marrow mesenchymal stromal cells of severe aplastic anemia patients attenuate hematopoietic functions of CD34+ hematopoietic stem and progenitor cells
    Srivastava, Jyotika
    Katiyar, Shobhita
    Chaturvedi, Chandra P.
    Nityanand, Soniya
    CELL BIOLOGY INTERNATIONAL, 2022, 46 (11) : 1970 - 1976
  • [13] Mesenchymal stem/stromal cells from human pluripotent stem cell-derived brain organoid enhance the ex vivo expansion and maintenance of hematopoietic stem/progenitor cells
    Zhou, Ya
    Cai, Xinping
    Zhang, Xiuxiu
    Dong, Yong
    Pan, Xu
    Lai, Mowen
    Zhang, Yimeng
    Chen, Yijin
    Li, Xiaohong
    Li, Xia
    Liu, Jiaxin
    Zhang, Yonggang
    Ma, Feng
    STEM CELL RESEARCH & THERAPY, 2024, 15 (01)
  • [14] EX-VIVO EXPANSION AND SUBSEQUENT INFUSION OF HUMAN BONE-MARROW-DERIVED STROMAL PROGENITOR CELLS (MESENCHYMAL PROGENITOR CELLS) - IMPLICATIONS FOR THERAPEUTIC USE
    LAZARUS, HM
    HAYNESWORTH, SE
    GERSON, SL
    ROSENTHAL, NS
    CAPLAN, AI
    BONE MARROW TRANSPLANTATION, 1995, 16 (04) : 557 - 564
  • [15] Characterization of human cardiac mesenchymal stromal cells and their extracellular vesicles comparing with human bone marrow derived mesenchymal stem cells
    Kang, In Sook
    Suh, Joowon
    Lee, Mi-Ni
    Lee, Chaeyoung
    Jin, Jing
    Lee, Changjin
    Yang, Young Il
    Jang, Yangsoo
    Oh, Goo Taeg
    BMB REPORTS, 2020, 53 (02) : 118 - 123
  • [16] Mesenchymal Stromal Cells from Perinatal Tissues as an Alternative for Ex Vivo Expansion of Hematopoietic Progenitor and Stem Cells from Umbilical Cord Blood
    Bonilla, Ximena
    Lara, Ana Milena
    Llano-Leon, Manuela
    Lopez-Gonzalez, David A.
    Hernandez-Mejia, David G.
    Bustos, Rosa Helena
    Camacho-Rodriguez, Bernardo
    Perdomo-Arciniegas, Ana-Maria
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023, 24 (21)
  • [17] Ex vivo Expansion and Differentiation of Mesenchymal Stem Cells from Goat Bone Marrow
    Eslaminejad, Mohamadreza Baghaban
    Nazarian, Hamid
    Falahi, Fahimeh
    Taghiyar, Leila
    Daneshzadeh, Mohamad Taghi
    IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, 2009, 12 (02) : 70 - 79
  • [18] Wharton's Jelly Mesenchymal Stromal Cells as a Feeder Layer for the Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells: a Review
    Lo Iacono, Melania
    Anzalone, Rita
    La Rocca, Giampiero
    Baiamonte, Elena
    Maggio, Aurelio
    Acuto, Santina
    STEM CELL REVIEWS AND REPORTS, 2017, 13 (01) : 35 - 49
  • [19] Wharton’s Jelly Mesenchymal Stromal Cells as a Feeder Layer for the Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells: a Review
    Melania Lo Iacono
    Rita Anzalone
    Giampiero La Rocca
    Elena Baiamonte
    Aurelio Maggio
    Santina Acuto
    Stem Cell Reviews and Reports, 2017, 13 : 35 - 49
  • [20] Ex vivo expansions and transplantations of mouse bone marrow-derived hematopoietic stem/progenitor cells
    Wang Jin-fu
    Wu Yi-fan
    Harrintong Jenny
    Ian K. McNiece
    Journal of Zhejiang University-SCIENCE A, 2004, 5 (2): : 157 - 163