MicroRNA Cargo in Wharton's Jelly MSC Small Extracellular Vesicles: Key Functionality to In Vitro Prevention and Treatment of Premature White Matter Injury.
Premature white matter injury
Wharton’s jelly mesenchymal stromal cells
microRNA
small extracellular vesicles
Journal
Stem cell reviews and reports
ISSN: 2629-3277
Titre abrégé: Stem Cell Rev Rep
Pays: United States
ID NLM: 101752767
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
accepted:
12
07
2023
medline:
23
10
2023
pubmed:
31
7
2023
entrez:
31
7
2023
Statut:
ppublish
Résumé
Preterm birth is the leading cause of childhood morbidity and mortality and can result in white matter injury (WMI), leading to long-term neurological disabilities with global health burden. Mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEV) are a promising therapeutic agent for treating perinatal neurological injury. They carry microRNAs (miRNAs) predicted to be involved in the onset of premature WMI. We hypothesize that miRNAs have a key function in the beneficial effects of MSC-sEV. We isolated MSC from umbilical cord tissue, the Wharton's jelly (WJ), and purified small extracellular vesicles (sEV) from WJ-MSC culture supernatant by ultracentrifugation and size exclusion chromatography. The miRNA content was quantified by real-time polymerase chain reaction. A luciferase gene assay validated silencing of TP53 and TAOK1, which we previously identified as predicted target genes of MSC-sEV miRNAs by Next Generation Sequencing and pathway enrichment analysis. The impact of sEV miRNAs on oligodendroglial maturation and neuronal apoptosis was evaluated using an in vitro oxygen-glucose deprivation model (OGD/R) by knocking-down DROSHA in WJ-MSC, which initiates miRNA processing. WJ-MSC-sEV contained miRNAs involved in WMI, namely hsa-miR-22-3p, hsa-miR-21-5p, hsa-miR-27b-3p, and the hsa-let-7 family. The luciferase assay strongly indicated an inhibitory effect of sEV miRNAs on the gene expression of TP53 and TAOK1. Small EV initiated oligodendrocyte maturation and reduced OGD/R-mediated neuronal apoptosis. Knocking-down DROSHA in WJ-MSC reduced the expression of sEV miRNAs and led to the loss of their beneficial effects. Our in vitro study strongly indicates the key function of miRNAs in the therapeutic potential of WJ-MSC-sEV in premature WMI.
Identifiants
pubmed: 37523115
doi: 10.1007/s12015-023-10595-1
pii: 10.1007/s12015-023-10595-1
pmc: PMC10579138
doi:
Substances chimiques
MicroRNAs
0
Luciferases
EC 1.13.12.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2447-2464Informations de copyright
© 2023. The Author(s).
Références
Nucleic Acids Res. 2023 Jan 6;51(D1):D217-D225
pubmed: 36453996
Cancer Gene Ther. 1998 Jan-Feb;5(1):52-63
pubmed: 9476967
Int J Neuropsychopharmacol. 2022 Apr 19;25(4):328-338
pubmed: 35015859
Handb Clin Neurol. 2019;162:155-172
pubmed: 31324309
Cell Death Differ. 2002 Oct;9(10):1031-42
pubmed: 12232790
Cell Death Dis. 2018 May 3;9(5):512
pubmed: 29724992
Stem Cell Res Ther. 2019 Mar 21;10(1):105
pubmed: 30898154
Nature. 1984 Mar 8-14;308(5955):199-201
pubmed: 6366574
Cell Metab. 2019 Oct 1;30(4):656-673
pubmed: 31447320
Blood. 2008 Feb 1;111(3):1217-26
pubmed: 17957028
Lancet Neurol. 2009 Jan;8(1):110-24
pubmed: 19081519
Nature. 2004 Nov 11;432(7014):231-5
pubmed: 15531879
J Extracell Vesicles. 2019 Apr 29;8(1):1609206
pubmed: 31069028
Cells. 2020 Oct 11;9(10):
pubmed: 33050562
Trends Cell Biol. 2023 Aug;33(8):667-681
pubmed: 36737375
Biology (Basel). 2021 Feb 25;10(3):
pubmed: 33668707
J Biol Chem. 2007 Mar 2;282(9):6484-93
pubmed: 17158878
Carcinogenesis. 2014 Aug;35(8):1680-90
pubmed: 24942866
J Transl Med. 2021 May 11;19(1):202
pubmed: 33975607
Brain Res. 2022 Nov 1;1794:148042
pubmed: 35952773
Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1881-9
pubmed: 26976605
Stem Cells Transl Med. 2016 Jun;5(6):754-63
pubmed: 27160705
J Extracell Vesicles. 2015 Oct 05;4:28665
pubmed: 26443722
Int J Mol Sci. 2020 Oct 10;21(20):
pubmed: 33050415
Trends Cell Biol. 2001 May;11(5):220-30
pubmed: 11316611
Front Cell Neurosci. 2020 Dec 10;14:601176
pubmed: 33362471
J Extracell Vesicles. 2014 Mar 26;3:
pubmed: 24683445
Nature. 2022 Jan;601(7893):446-451
pubmed: 34937935
Curr Protoc Cell Biol. 2006 Apr;Chapter 3:Unit 3.22
pubmed: 18228490
Cell. 1993 Dec 3;75(5):843-54
pubmed: 8252621
Bio Protoc. 2019 Jan 5;9(1):
pubmed: 30687773
Neuron. 1998 Jul;21(1):63-75
pubmed: 9697852
Mol Immunol. 2020 Apr 25;122:124-131
pubmed: 32344244
Front Endocrinol (Lausanne). 2018 Aug 03;9:402
pubmed: 30123182
J Cell Biol. 1983 Aug;97(2):329-39
pubmed: 6309857
Adv Drug Deliv Rev. 2020;159:332-343
pubmed: 32305351
Glia. 2019 Jul;67(7):1320-1332
pubmed: 30815939
Cytotherapy. 2006;8(4):315-7
pubmed: 16923606
Mol Neurobiol. 2014 Feb;49(1):113-9
pubmed: 23857502
J Cell Biol. 1985 Sep;101(3):942-8
pubmed: 2993317
Neonatology. 2022;119(3):345-353
pubmed: 35340004
Cell Transplant. 2018 Jan;27(1):168-180
pubmed: 29562785
Nat Cell Biol. 2007 Jun;9(6):654-9
pubmed: 17486113
Acta Biomater. 2020 Sep 1;113:597-613
pubmed: 32619670
ACS Omega. 2020 Jun 30;5(27):16701-16710
pubmed: 32685837
Cell. 2015 Nov 5;163(4):811-28
pubmed: 26544935
Pharmaceutics. 2020 Feb 21;12(2):
pubmed: 32098213
Stem Cells. 2023 Mar 2;41(2):169-183
pubmed: 36512434
Ann Neurol. 2011 May;69(5):743-58
pubmed: 21520238
Int J Biol Sci. 2022 Aug 21;18(14):5345-5368
pubmed: 36147480
J Mol Cell Biol. 2023 Mar 29;14(10):
pubmed: 36565718
PLoS One. 2013 Sep 20;8(9):e75184
pubmed: 24073250
Pharmaceutics. 2019 Aug 11;11(8):
pubmed: 31405234
Nature. 2012 Dec 20;492(7429):376-81
pubmed: 23222520
Science. 2019 Dec 20;366(6472):
pubmed: 31806698
Genes Dev. 2004 Dec 15;18(24):3016-27
pubmed: 15574589
Front Physiol. 2019 Mar 19;10:282
pubmed: 30941062
Apoptosis. 2008 Oct;13(10):1215-22
pubmed: 18758960
Cell Death Differ. 2018 Jan;25(1):104-113
pubmed: 29149101
Nat Genet. 2003 Nov;35(3):215-7
pubmed: 14528307
Cells. 2019 Aug 08;8(8):
pubmed: 31398924
RNA Biol. 2018 Feb 1;15(2):186-193
pubmed: 29171328
J Biol Chem. 2006 Mar 17;281(11):7317-23
pubmed: 16407310
Sci Transl Med. 2019 May 15;11(492):
pubmed: 31092696
Front Cell Dev Biol. 2021 Mar 23;9:622539
pubmed: 33869172
Inflamm Regen. 2023 Apr 17;43(1):24
pubmed: 37069694