Functional Effects of Delivering Human Mesenchymal Stem Cell-Seeded Biological Sutures to an Infarcted Heart.
Stem cell therapy has the potential to improve cardiac function after myocardial infarction (MI); however, existing methods to deliver cells to the myocardium, including intramyocardial injection, suffer from low engraftment rates. In this study, we used a rat model of acute MI to assess the effects of human mesenchymal stem cell (hMSC)-seeded fibrin biological sutures on cardiac function at 1 week after implant. Biological sutures were seeded with quantum dot (Qdot)-loaded hMSCs for 24 h before implantation. At 1 week postinfarct, the heart was imaged to assess mechanical function in the infarct region. Regional parameters assessed were regional stroke work (RSW) and systolic area of contraction (SAC) and global parameters derived from the pressure waveform. MI (n = 6) significantly decreased RSW (0.026 ± 0.011) and SAC (0.022 ± 0.015) when compared with sham operation (RSW: 0.141 ± 0.009; SAC: 0.166 ± 0.005, n = 6) (p < 0.05). The delivery of unseeded biological sutures to the infarcted hearts did not change regional mechanical function compared with the infarcted hearts (RSW: 0.032 ± 0.004, SAC: 0.037 ± 0.008, n = 6). The delivery of hMSC-seeded sutures exerted a trend toward increase of regional mechanical function compared with the infarcted heart (RSW: 0.057 ± 0.011; SAC: 0.051 ± 0.014, n = 6). Global function showed no significant differences between any group (p > 0.05); however, there was a trend toward improved function with the addition of either unseeded or seeded biological suture. Histology demonstrated that Qdot-loaded hMSCs remained present in the infarcted myocardium after 1 week. Analysis of serial sections of Masson's trichrome staining revealed that the greatest infarct size was in the infarct group (7.0% ± 2.2%), where unseeded (3.8% ± 0.6%) and hMSC-seeded (3.7% ± 0.8%) suture groups maintained similar infarct sizes. Furthermore, the remaining suture area was significantly decreased in the unseeded group compared with that in the hMSC-seeded group (p < 0.05). This study demonstrated that hMSC-seeded biological sutures are a method to deliver cells to the infarcted myocardium and have treatment potential.
Department of Biomedical Engineering, Worcester Polytechnic Institute , Worcester, Massachusetts.
Katrina J
KJ
Hansen
Department of Biomedical Engineering, Worcester Polytechnic Institute , Worcester, Massachusetts.
John T
JT
Favreau
Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts.; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Jacques P
JP
Guyette
Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts.; Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Ze-Wei
ZW
Tao
Department of Biomedical Engineering, Worcester Polytechnic Institute , Worcester, Massachusetts.
Spencer T
ST
Coffin
Department of Biomedical Engineering, Worcester Polytechnic Institute , Worcester, Massachusetts.
Anny
A
Cunha-Gavidia
Department of Biomedical Engineering, Worcester Polytechnic Institute , Worcester, Massachusetts.
Brian
B
D'Amore
Department of Biomedical Engineering, Worcester Polytechnic Institute , Worcester, Massachusetts.
Luke R
LR
Perreault
Department of Biomedical Engineering, Worcester Polytechnic Institute , Worcester, Massachusetts.
John P
JP
Fitzpatrick
Department of Biomedical Engineering, Worcester Polytechnic Institute , Worcester, Massachusetts.
Angelica
A
DeMartino
Department of Biomedical Engineering, Worcester Polytechnic Institute , Worcester, Massachusetts.
Glenn R
GR
Gaudette
biomaterials; cardiology; stem cells; tissue engineering