IFATS collection: Human adipose tissue-derived stem cells induce angiogenesis and nerve sprouting following myocardial infarction, in conjunction with potent preservation of cardiac function.
The administration of therapeutic cell types, such as stem and progenitor cells, has gained much interest for the limitation or repair of tissue damage caused by a variety of insults. However, it is still uncertain whether the morphological and functional benefits are mediated predominantly via cell differentiation or paracrine mechanisms. Here, we assessed the extent and mechanisms of adipose-derived stromal/stem cells (ASC)-dependent tissue repair in the context of acute myocardial infarction. Human ASCs in saline or saline alone was injected into the peri-infarct region in athymic rats following left anterior descending (LAD) coronary artery ligation. Cardiac function and structure were evaluated by serial echocardiography and histology. ASC-treated rats consistently exhibited better cardiac function, by all measures, than control rats 1 month following LAD occlusion. Left ventricular (LV) ejection fraction and fractional shortening were improved in the ASC group, whereas LV remodeling and dilation were limited in the ASC group compared with the saline control group. Anterior wall thinning was also attenuated by ASC treatment, and post-mortem histological analysis demonstrated reduced fibrosis in ASC-treated hearts, as well as increased peri-infarct density of both arterioles and nerve sprouts. Human ASCs were persistent at 1 month in the peri-infarct region, but they were not observed to exhibit significant cardiomyocyte differentiation. Human ASCs preserve heart function and augment local angiogenesis and cardiac nerve sprouting following myocardial infarction predominantly by the provision of beneficial trophic factors.
Cai
Liying
L
Indiana Center for Vascular Biology and Medicine, Indiana University School of Medicine, Indianapolis, USA.
Johnstone
Brian H
BH
Cook
Todd G
TG
Tan
Jian
J
Fishbein
Michael C
MC
Chen
Peng-Sheng
PS
March
Keith L
KL
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002470:Cell Survival; D005260:Female; D006321:Heart / Q000294:innervation / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D055806:Microvessels / Q000503:physiopathology; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D018919:Neovascularization, Physiologic; D055495:Neurogenesis; D051381:Rats; D020127:Recovery of Function; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D014463:Ultrasonography
Biochem Biophys Res Commun. 1991 Sep 16;179(2):1042-9
1654897
Circulation. 2006 Mar 14;113(10):1287-94
16520413
Hum Pathol. 1991 Feb;22(2):138-46
1705914
Circulation. 2004 Jul 20;110(3):349-55
15238461
Circ Res. 2000 Apr 14;86(7):816-21
10764417
Arterioscler Thromb Vasc Biol. 2005 Dec;25(12):2542-7
16224047
Circulation. 2001 Jan 2;103(1):22-5
11136680
J Atheroscler Thromb. 2006 Apr;13(2):77-81
16733294
Cell. 2003 Sep 19;114(6):763-76
14505575
Transplant Proc. 1997 Feb-Mar;29(1-2):569-70
9123132
J Heart Lung Transplant. 2004 Dec;23(12):1349-58
15607663
Biochem Biophys Res Commun. 2007 Mar 23;354(4):999-1003
17276389
Biochem Biophys Res Commun. 2005 Jul 1;332(2):370-9
15896706
Stem Cells. 2007 Dec;25(12):3234-43
17901400
Circulation. 1995 Jan 1;91(1):72-8
7646628
Lancet. 2004 Mar 6;363(9411):751-6
15016484
Circulation. 2004 Feb 10;109(5):656-63
14734516
Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8966-71
15951423
Biochem Biophys Res Commun. 2007 Nov 23;363(3):674-9
17904522
Coron Artery Dis. 2007 May;18(3):221-7
17429297
Cell Mol Biol (Noisy-le-grand). 1995 Sep;41(6):799-807
8535173
Circ Res. 2004 Jul 9;95(1):76-83
15166093
J Thorac Cardiovasc Surg. 2003 Feb;125(2):361-9
12579106
Circulation. 2002 Dec 10;106(24):3009-17
12473544
J Cardiovasc Electrophysiol. 2003 Aug;14(8):841-8
12890047
J Cell Biol. 1992 Nov;119(3):629-41
1383237
Circulation. 2007 Jul 24;116(4):366-74
17620510
Arch Intern Med. 2007 May 28;167(10):989-97
17533201
N Engl J Med. 1996 Oct 17;335(16):1182-9
8815940
Lab Invest. 1990 Oct;63(4):490-501
2232703
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3422-7
10725398
Circulation. 2001 Apr 10;103(14):1881-6
11294807
Am J Cardiol. 1996 Jan 1;77(1):5-9
8540457
Circulation. 2004 Mar 16;109(10):1292-8
14993122
Gynecol Oncol. 1999 Aug;74(2):245-51
10419739
Circulation. 2003 Sep 9;108 Suppl 1:II253-8
12970242
Circulation. 1985 Sep;72(3):623-31
4017213
Circ Res. 2005 Sep 30;97(7):663-73
16141414
Circ Res. 2004 Feb 6;94(2):223-9
14656930
Cytotherapy. 2005;7(3):282-91
16081355
Circulation. 1997 Jan 21;95(2):320-3
9008443
Cardiovasc Res. 2001 Jul;51(1):41-50
11399246
J Am Coll Cardiol. 2007 Oct 30;50(18):1761-7
17964040
Europace. 2007 Dec;9(12):1218-21
17951268
Circulation. 2000 Apr 25;101(16):1960-9
10779463
J Clin Invest. 2006 Jan;116(1):237-48
16357943
J Cardiovasc Electrophysiol. 2001 Sep;12(9):1068-73
11573698