Stem cell-derived exosomes as a therapeutic tool for cardiovascular disease.
Mesenchymal stem cells (MSCs) have been used to treat patients suffering from acute myocardial infarction (AMI) and subsequent heart failure. Although it was originally assumed that MSCs differentiated into heart cells such as cardiomyocytes, recent evidence suggests that the differentiation capacity of MSCs is minimal and that injected MSCs restore cardiac function via the secretion of paracrine factors. MSCs secrete paracrine factors in not only naked forms but also membrane vesicles including exosomes containing bioactive substances such as proteins, messenger RNAs, and microRNAs. Although the details remain unclear, these bioactive molecules are selectively sorted in exosomes that are then released from donor cells in a regulated manner. Furthermore, exosomes are specifically internalized by recipient cells via ligand-receptor interactions. Thus, exosomes are promising natural vehicles that stably and specifically transport bioactive molecules to recipient cells. Indeed, stem cell-derived exosomes have been successfully used to treat cardiovascular disease (CVD), such as AMI, stroke, and pulmonary hypertension, in animal models, and their efficacy has been demonstrated. Therefore, exosome administration may be a promising strategy for the treatment of CVD. Furthermore, modifications of exosomal contents may enhance their therapeutic effects. Future clinical studies are required to confirm the efficacy of exosome treatment for CVD.
Etsu Suzuki, Institute of Medical Science, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki 216-8512, Japan.
Etsu
E
Suzuki
Etsu Suzuki, Institute of Medical Science, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki 216-8512, Japan.
Daishi
D
Fujita
Etsu Suzuki, Institute of Medical Science, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki 216-8512, Japan.
Masao
M
Takahashi
Etsu Suzuki, Institute of Medical Science, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki 216-8512, Japan.
Shigeyoshi
S
Oba
Etsu Suzuki, Institute of Medical Science, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki 216-8512, Japan.
Hiroaki
H
Nishimatsu
Cardiovascular disease; Exosomes; Mesenchymal stem cells; Messenger RNA; MicroRNA; Stem cells
Circ Res. 2011 May 27;108(11):1340-7
21493893
Biochim Biophys Acta. 2009 Dec;1793(12 ):1901-16
19781582
Biomaterials. 2014 Feb;35(7):2383-90
24345736
J Extracell Vesicles. 2012 Apr 16;1:null
24009880
Nucleic Acids Res. 2012 Sep 1;40(17):e130
22618874
Stem Cell Res. 2010 May;4(3):214-22
20138817
Proc Natl Acad Sci U S A. 2003 May 27;100(11):6670-5
12743365
Blood. 2004 Nov 15;104(10):3257-66
15284116
J Immunol. 2011 Feb 15;186(4):2219-28
21242526
Cold Spring Harb Protoc. 2015 Apr 01;2015(4):319-23
25834266
Stem Cells Dev. 2009 Jun;18(5):683-92
19099374
Chembiochem. 2014 May 5;15(7):923-8
24740901
Nat Cell Biol. 2007 Jun;9(6):654-9
17486113
PLoS One. 2014 Feb 18;9(2):e88685
24558412
J Neurooncol. 2013 May;113(1):1-11
23456661
J Mol Cell Cardiol. 2014 Mar;68:75-8
24440457
J Extracell Vesicles. 2012 Apr 16;1:null
24009886
Stem Cells. 2013 Dec;31(12):2737-46
23630198
Nat Med. 2005 Apr;11(4):367-8
15812508
Science. 1997 Feb 14;275(5302):964-7
9020076
Cell. 2001 Jul 27;106(2):145-55
11511343
Circulation. 2012 Nov 27;126(22):2601-11
23114789
J Am Coll Cardiol. 2009 Dec 8;54(24):2277-86
19958962
J Transl Med. 2005 Feb 21;3(1):9
15723705
Nat Cell Biol. 2010 Jan;12 (1):19-30; sup pp 1-13
19966785
Mol Cancer. 2014 Apr 26;13:88
24766647
Science. 2008 Feb 29;319(5867):1244-7
18309083
Cancer Lett. 2012 Feb 1;315(1):28-37
22055459
J Control Release. 2014 Oct 28;192:262-70
25084218
Am Heart J. 2011 Jun;161(6):1078-87.e3
21641354
J Biol Chem. 2013 Apr 26;288(17):11649-61
23463506
FEBS J. 2014 May;281(9):2214-27
24605801
J Korean Med Sci. 2014 Jan;29(1):23-31
24431901
Biochim Biophys Acta. 2015 Jan;1852(1):1-11
25463630
J Thromb Haemost. 2016 Jan;14 (1):48-56
26564379
J Mol Med (Berl). 2014 Apr;92(4):387-97
24337504
Proteomics. 2009 Nov;9(21):4997-5000
19810033
Science. 2008 Feb 29;319(5867):1191-2
18309064
Cardiovasc Res. 2014 Sep 1;103(4):530-41
25016614
J Cereb Blood Flow Metab. 2013 Nov;33(11):1711-5
23963371
Int J Cardiol. 2015 Mar 1;182:349-60
25590961
J Am Coll Cardiol. 2013 Jun 11;61(23):2329-38
23583246
Semin Cancer Biol. 2014 Oct;28:3-13
24769058
Biochem Pharmacol. 2012 Jun 1;83(11):1484-94
22230477
J Cell Biol. 2010 Apr 19;189(2):223-32
20404108
Mol Ther. 2013 Jan;21(1):185-91
23032975
Int J Mol Med. 2015 Jul;36(1):11-7
25902369
Mol Ther. 2010 Sep;18(9):1606-14
20571541
J Biol Chem. 2009 Dec 4;284(49):34211-22
19801663
Nat Biotechnol. 2011 Apr;29(4):341-5
21423189
Stem Cell Res. 2013 May;10 (3):301-12
23399448
J Cell Sci. 2002 Jun 15;115(Pt 12):2505-15
12045221
Ann Thorac Surg. 2002 Jun;73(6):1919-25; discussion 1926
12078791
Curr Opin Cell Biol. 2014 Aug;29:116-25
24959705
Nat Commun. 2013;4:2980
24356509
Circ Res. 2015 Jun 19;117(1):52-64
25904597
J Mol Biol. 2016 Feb 22;428(4):688-92
26434508
Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11474-9
16061805
J Biol Chem. 2003 May 30;278(22):20083-90
12639953
Biomaterials. 2014 May;35(14):4390-400
24565517
Vascul Pharmacol. 2015 Aug;71:24-30
25869502
FASEB J. 2006 Apr;20(6):661-9
16581974
Mov Disord. 2014 Oct;29(12):1476-85
25112864
Circulation. 2002 Jan 1;105(1):93-8
11772882
Nat Rev Immunol. 2009 Aug;9(8):581-93
19498381
Biochem Biophys Res Commun. 2013 Feb 15;431(3):566-71
23318173
J Mol Cell Cardiol. 2014 Sep;74:139-50
24825548
Circ Res. 2011 Sep 16;109(7):724-8
21835908
Circ Res. 2012 Jul 20;111(3):312-21
22581926
Mol Ther. 2011 Oct;19(10):1769-79
21915101
Cancer Res. 2010 Feb 15;70(4):1668-78
20124479
Eur Heart J. 2006 May;27(9):1114-22
16510464
Am J Cardiol. 2004 Jul 1;94(1):92-5
15219514
JAMA. 2012 Dec 12;308(22):2369-79
23117550
Stem Cell Reports. 2014 May 08;2(5):606-19
24936449
J Transl Med. 2005 Mar 02;3(1):10
15740633
Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1643-8
17251350
Mol Ther. 2008 Apr;16(4):782-90
18362931
Eur Heart J. 2009 Nov;30(22):2722-32
19586959