title: Delivering stem cells to the healthy heart on biological sutures: effects on regional mechanical function.
abstract: Current cardiac cell therapies cannot effectively target and retain cells in a specific area of the heart. Cell-seeded biological sutures were previously developed to overcome this limitation, demonstrating targeted delivery with > 60% cell retention. In this study, both cell-seeded and non-seeded fibrin-based biological sutures were implanted into normal functioning rat hearts to determine the effects on mechanical function and fibrotic response. Human mesenchymal stem cells (hMSCs) were used based on previous work and established cardioprotective effects. Non-seeded or hMSC-seeded sutures were implanted into healthy athymic rat hearts. Before cell seeding, hMSCs were passively loaded with quantum dot nanoparticles. One week after implantation, regional stroke work index and systolic area of contraction (SAC) were evaluated on the epicardial surface above the suture. Cell delivery and retention were confirmed by quantum dot tracking, and the fibrotic tissue area was evaluated. Non-seeded biological sutures decreased SAC near the suture from 0.20 ± 0.01 measured in sham hearts to 0.08 ± 0.02, whereas hMSC-seeded biological sutures dampened the decrease in SAC (0.15 ± 0.02). Non-seeded sutures also displayed a small amount of fibrosis around the sutures (1.0 ± 0.1 mm2). Sutures seeded with hMSCs displayed a significant reduction in fibrosis (0.5 ± 0.1 mm2, p < 0.001), with quantum dot-labelled hMSCs found along the suture track. These results show that the addition of hMSCs attenuates the fibrotic response observed with non-seeded sutures, leading to improved regional mechanics of the implantation region. Copyright © 2014 John Wiley & Sons, Ltd.
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
authors.forename: Ze-Wei
authors.initials: ZW
authors.lastname: Tao
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Favreau
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Guyette
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
authors.forename: Katrina J
authors.initials: KJ
authors.lastname: Hansen
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lessard
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
authors.forename: Evans
authors.initials: E
authors.lastname: Burford
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
authors.forename: George D
authors.initials: GD
authors.lastname: Pins
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Gaudette
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D017690:Cell Transplantation; D005337:Fibrin / Q000494:pharmacology; D005355:Fibrosis; D006321:Heart / Q000502:physiology*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D045663:Quantum Dots; D051381:Rats; D011923:Rats, Nude; D013314:Stress, Mechanical; D013537:Sutures; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D005337:Fibrin
keywords: biological sutures; cardiac biomechanics; mechanical function; stem cells; tissue regeneration; wound healing
references.citation: J Cardiovasc Pharmacol Ther. 2013 May;18(3):270-9
references.pmid: 23345062
references.citation: J Am Coll Cardiol. 2009 Oct 20;54(17):1619-26
references.pmid: 19833262
references.citation: Circulation. 2005 Jul 12;112(2):214-23
references.pmid: 15998673
references.citation: Kidney Int. 2006 Jul;70(1):121-9
references.pmid: 16723981
references.citation: J Am Coll Cardiol. 2006 Apr 18;47(8):1672-82
references.pmid: 16631008
references.citation: Circulation. 2003 Aug 19;108(7):863-8
references.pmid: 12900340
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8407-11
references.pmid: 12815096
references.citation: J Biomed Mater Res A. 2007 Jul;82(1):104-12
references.pmid: 17269139
references.citation: Am J Physiol Heart Circ Physiol. 2009 Jul;297(1):H257-67
references.pmid: 19395547
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11474-9
references.pmid: 16061805
references.citation: J Cell Mol Med. 2009 Nov-Dec;13(11-12):4385-402
references.pmid: 19602034
references.citation: Circulation. 2005 Aug 30;112(9 Suppl):I150-6
references.pmid: 16159808
references.citation: J Zhejiang Univ Sci B. 2010 Apr;11(4):238-48
references.pmid: 20349520
references.citation: Ann N Y Acad Sci. 2001;936:355-67
references.pmid: 11460492
references.citation: Stem Cells Dev. 2009 Mar;18(2):321-9
references.pmid: 18435573
references.citation: J Zhejiang Univ Sci. 2004 Apr;5(4):494-8
references.pmid: 14994444
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):14022-7
references.pmid: 19666564
references.citation: Am J Physiol Heart Circ Physiol. 2012 Sep 1;303(5):H549-58
references.pmid: 22777422
references.citation: Med Eng Phys. 2007 Jan;29(1):154-62
references.pmid: 16531092
references.citation: Nature. 2002 Jul 4;418(6893):41-9
references.pmid: 12077603
references.citation: J Am Coll Cardiol. 2004 Aug 4;44(3):654-60
references.pmid: 15358036
references.citation: J Am Coll Cardiol. 2009 Jun 16;53(24):2262-9
references.pmid: 19520249
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10344-9
references.pmid: 11504914
references.citation: J Biomed Mater Res A. 2013 Mar;101(3):809-18
references.pmid: 22961975
references.citation: Clin Biochem. 2007 Aug;40(12):893-9
references.pmid: 17543295
references.citation: J Hepatol. 2006 Apr;44(4):742-8
references.pmid: 16469408
references.citation: J Perinatol. 2005 Nov;25(11):720-4
references.pmid: 16163366
references.citation: Lancet. 2004 Jul 10-16;364(9429):141-8
references.pmid: 15246726
references.citation: J Biomed Mater Res A. 2011 Feb;96(2):301-12
references.pmid: 21171149
references.citation: J Mol Cell Cardiol. 2012 May;52(5):1083-90
references.pmid: 22418281
references.citation: Blood. 2005 Feb 15;105(4):1815-22
references.pmid: 15494428
references.citation: Sci Transl Med. 2013 Feb 20;5(173):173ra25
references.pmid: 23427245
references.citation: Circulation. 2005 Aug 23;112(8):1128-35
references.pmid: 16103243
references.citation: N Engl J Med. 2006 Sep 21;355(12):1210-21
references.pmid: 16990384
references.citation: Tissue Eng. 2004 Mar-Apr;10(3-4):403-9
references.pmid: 15165457
references.citation: Biomaterials. 2011 Aug;32(24):5558-67
references.pmid: 21555151
references.citation: Tissue Eng Part A. 2008 Jun;14(6):1025-36
references.pmid: 18476809
references.citation: Stem Cells. 2007 Aug;25(8):2128-38
references.pmid: 17495112
references.citation: Eur J Heart Fail. 2009 Jan;11(1):14-9
references.pmid: 19147452
references.citation: Blood. 2011 Jan 27;117(4):1176-83
references.pmid: 21076046
references.citation: IEEE Trans Ultrason Ferroelectr Freq Control. 2008 Jan;55(1):240-8
references.pmid: 18334330
references.citation: PLoS One. 2012;7(1):e29202
references.pmid: 22238593