Hypoxic Conditions Promote the Angiogenic Potential of Human Induced Pluripotent Stem Cell-Derived Extracellular Vesicles.
angiogenesis
extracellular vesicles (EV)
hypoxia
hypoxia-inducible transcription factor (HIF)
induced pluripotent stem cells (iPSC)
regenerative medicine
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
09 Apr 2021
09 Apr 2021
Historique:
received:
26
03
2021
revised:
06
04
2021
accepted:
07
04
2021
entrez:
30
4
2021
pubmed:
1
5
2021
medline:
26
5
2021
Statut:
epublish
Résumé
Stem cells secrete paracrine factors including extracellular vesicles (EVs) which can mediate cellular communication and support the regeneration of injured tissues. Reduced oxygen (hypoxia) as a key regulator in development and regeneration may influence cellular communication via EVs. We asked whether hypoxic conditioning during human induced pluripotent stem cell (iPSC) culture effects their EV quantity, quality or EV-based angiogenic potential. We produced iPSC-EVs from large-scale culture-conditioned media at 1%, 5% and 18% air oxygen using tangential flow filtration (TFF), with or without subsequent concentration by ultracentrifugation (TUCF). EVs were quantified by tunable resistive pulse sensing (TRPS), characterized according to MISEV2018 guidelines, and analyzed for angiogenic potential. We observed superior EV recovery by TFF compared to TUCF. We confirmed hypoxia efficacy by HIF-1α stabilization and pimonidazole hypoxyprobe. EV quantity did not differ significantly at different oxygen conditions. Significantly elevated angiogenic potential was observed for iPSC-EVs derived from 1% oxygen culture by TFF or TUCF as compared to EVs obtained at higher oxygen or the corresponding EV-depleted soluble factor fractions. Data thus demonstrate that cell-culture oxygen conditions and mode of EV preparation affect iPSC-EV function. We conclude that selecting appropriate protocols will further improve production of particularly potent iPSC-EV-based therapeutics.
Identifiants
pubmed: 33918735
pii: ijms22083890
doi: 10.3390/ijms22083890
pmc: PMC8070165
pii:
doi:
Substances chimiques
Biomarkers
0
Hypoxia-Inducible Factor 1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Seventh Framework Programme
ID : 733006
Organisme : Horizon 2020 Framework Programme
ID : 731377
Références
Exp Ther Med. 2018 Jun;15(6):4791-4797
pubmed: 29805497
Blood. 2007 Jun 1;109(11):4761-8
pubmed: 17327403
J Vis Exp. 2009 Oct 28;(32):
pubmed: 19861942
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Science. 2020 Feb 7;367(6478):
pubmed: 32029601
Nat Rev Mol Cell Biol. 2018 Apr;19(4):213-228
pubmed: 29339798
Stem Cells Transl Med. 2021 Mar 4;:
pubmed: 33660952
Int J Mol Sci. 2021 Feb 26;22(5):
pubmed: 33652743
Int J Mol Sci. 2020 May 25;21(10):
pubmed: 32466282
Int J Mol Sci. 2019 Mar 08;20(5):
pubmed: 30857245
Front Physiol. 2018 Dec 14;9:1794
pubmed: 30618806
Am J Physiol Heart Circ Physiol. 2021 Mar 1;320(3):H954-H968
pubmed: 33416449
J Neuroimmune Pharmacol. 2020 Sep;15(3):520-537
pubmed: 31338754
Stem Cells Transl Med. 2016 Oct;5(10):1289-1301
pubmed: 27369897
Biomaterials. 2016 Jan;76:371-87
pubmed: 26561934
Front Cell Dev Biol. 2017 Sep 29;5:88
pubmed: 29034231
Int J Biol Sci. 2019 Jan 1;15(1):158-168
pubmed: 30662356
Stem Cell Res Ther. 2020 Jul 22;11(1):313
pubmed: 32698909
Oncogene. 2017 Sep 21;36(38):5331-5340
pubmed: 28534514
EBioMedicine. 2019 Apr;42:443-457
pubmed: 30926422
Cell Stem Cell. 2010 Aug 6;7(2):150-61
pubmed: 20682444
Eur Heart J. 2018 May 21;39(20):1835-1847
pubmed: 29420830
Clin Transl Med. 2020 Dec;10(8):e262
pubmed: 33377658
Leukemia. 2014 Apr;28(4):970-3
pubmed: 24445866
Nature. 2004 Mar 11;428(6979):138-9
pubmed: 15014486
Int J Mol Sci. 2021 Jan 19;22(2):
pubmed: 33478018
Nat Med. 2020 Oct;26(10):1519-1530
pubmed: 33020645
Stem Cells Transl Med. 2021 Mar;10(3):414-426
pubmed: 33174379
J Extracell Vesicles. 2015 Dec 31;4:30087
pubmed: 26725829
Am J Physiol Heart Circ Physiol. 2019 Oct 1;317(4):H765-H776
pubmed: 31418583
PLoS One. 2013 Jun 24;8(6):e66909
pubmed: 23826172
Pharmacol Ther. 2017 Mar;171:30-42
pubmed: 27916653
Nat Biotechnol. 2014 Nov;32(11):1151-1157
pubmed: 25306246
Int J Mol Sci. 2017 Jul 01;18(7):
pubmed: 28671586
Curr Opin Organ Transplant. 2010 Feb;15(1):68-72
pubmed: 19898235
Blood. 2009 Jun 25;113(26):6716-25
pubmed: 19321860
J Vis Exp. 2009 Oct 08;(32):
pubmed: 19816400
J Control Release. 2019 Jul 28;306:108-120
pubmed: 31175896
Sci Transl Med. 2020 Sep 16;12(561):
pubmed: 32938792
PLoS One. 2012;7(9):e44468
pubmed: 22970226
Stem Cell Res Ther. 2015 Dec 01;6:236
pubmed: 26620155
Tissue Eng Part C Methods. 2008 Sep;14(3):185-96
pubmed: 18620484
Circ Res. 2018 Jan 19;122(2):296-309
pubmed: 29118058
Int J Cardiol. 2015 Aug 1;192:61-9
pubmed: 26000464
J Extracell Vesicles. 2018 Nov 23;7(1):1535750
pubmed: 30637094
Arch Cardiovasc Dis. 2020 Apr;113(4):285-292
pubmed: 32171698
Stem Cell Res Ther. 2021 Feb 12;12(1):131
pubmed: 33579366
Stem Cell Reports. 2018 May 8;10(5):1657-1672
pubmed: 29681541
Hum Mol Genet. 2012 Oct 15;21(R1):R125-34
pubmed: 22872698
Annu Rev Pharmacol Toxicol. 2019 Jan 6;59:379-403
pubmed: 30625281
Stem Cell Reports. 2020 Sep 8;15(3):735-748
pubmed: 32763163
Int J Biol Sci. 2017 Feb 6;13(2):232-244
pubmed: 28255275
J Transl Med. 2015 Feb 01;13:49
pubmed: 25638205
Nat Biotechnol. 2021 Feb 8;:
pubmed: 33558697
Free Radic Biol Med. 2017 Dec;113:311-322
pubmed: 29032224
Int J Biol Sci. 2016 May 25;12(7):836-49
pubmed: 27313497
Stem Cell Res Ther. 2015 Apr 10;6:10
pubmed: 26268554