| Title: |
Tissue Engineering and Repair of the Damaged Heart |
| Authors: |
Madonna, R; Taylor, D; Lyubomir, P; Gobin, AS; Geng, YJ; Ferdinandy, P; De Caterina, R; Cabriera, M; Perin, E; Willerson, JT; Robertson, A; Mohammed, T; Cartwright, E; Oceandy, D; Campagnolo, P; Chiappini, C; Leonardo, V; Becce, M; Perbellini, F; Terracciano, C; Smart, N; Harding, SA; Stevens, MM |
| Publisher Information: |
Oxford University Press |
| Publication Year: |
2016 |
| Collection: |
HighWire Press (Stanford University) |
| Subject Terms: |
Sunday 10 July 2016 |
| Description: |
Rationale: The success of stem cell therapies for acute myocardial infarction (AMI) has been hampered by poor cellular engraftment and survival, which may be partly due to the harmful microenvironment within ischemic myocardium. However, it may be possible to promote survival and cardiomyogenesis of transplanted adult mesenchymal cells by inducing the overexpression of myocardin (MYOCD), a promyogenic transcription factor with anti-apoptotic activity, and telomerase reverse transcriptase (TERT), an antisenescence protein. Objectives: We used a murine model of AMI to assess the efficacy of transplanted adipose tissue-derived mesenchymal stromal cells (AT-MSCs) engineered to overexpress MYOCD and TERT. Methods: Twelve-month-old C57BL/6 mice underwent coronary artery ligation to induce AMI and were randomized into 3 treatment groups: phosphate-buffered saline (PBS) (20µL; n=7), mock-transduced AT-MSCs (2.5x105 cells in 20µL; n=5), or AT-MSCs overexpressing TERT and MYOCD (2.5x105 cells in 20µL; n=7). Sham-operated mice (n=7) were used as controls. The AT-MSCs were obtained from 12-month-old male green fluorescent protein-transgenic C57BL/6 mice and transduced with lentiviral vectors encoding TERT and MYOCD. Results: When transplanted into the infarcted hearts of C57BL/6 mice, AT-MSCs overexpressing TERT and MYOCD preserved myocardial fractional shortening (Figure A), increased arteriogenesis and cell engraftment and decreased fibrosis formation (Figure B), compared with PBS alone or mock-transduced AT-MSCs. These effects were accompanied by increased numbers of Ki-67+ cells and c-kit+ cells (Figure B) and enhanced expression of cardiac actin, GATA4, Nkx2.5, and myocardin A (Figure C). Conclusions: Delivering TERT and MYOCD genes into AT-MSCs before transplantation promotes activation of the cardiomyogenic pathway, vasculogenesis, and stem cell survival in a murine model of AMI. |
| Document Type: |
text |
| File Description: |
text/html |
| Language: |
English |
| Relation: |
http://cardiovascres.oxfordjournals.org/cgi/content/short/111/suppl_1/S87; http://dx.doi.org/10.1093/cvr/cvw153 |
| DOI: |
10.1093/cvr/cvw153 |
| Availability: |
http://cardiovascres.oxfordjournals.org/cgi/content/short/111/suppl_1/S87; https://doi.org/10.1093/cvr/cvw153 |
| Rights: |
Copyright (C) 2016, European Society of Cardiology |
| Accession Number: |
edsbas.4FA97B87 |
| Database: |
BASE |