Author + information
- Yen-Wen Liu,
- Mineo Iwata,
- Elina Minami,
- Kraig Abrams and
- Beverly Torok-Storb
Background: Reports of cell-based cardiac repair have been inconsistent, particularly in response to infusion of marrow cells. Variability in efficacy may be due in part to heterogeneity in the cells infused. Thus, we used an immortalized and cloned population of canine marrow fibroblasts (DS-1) as a consistent therapeutic infused at 2 weeks after myocardial infarction (MI) in a canine model.
Methods: To induce MI, we inflated an angioplasty balloon at the mid-left anterior descending coronary artery to totally occlude dogs’ coronary blood flow for 90 minutes. MI was documented by the increased serum cardiac troponin levels, ST segment elevation of ECG and coronary angiography. At post-MI 2 weeks, dogs were infused intravenously with either vehicle (as control) or DS-1 cells (107 cells / kg). We did cardiac magnetic resonance imaging (CMR) at post-MI 2 weeks (prior to treatment) and 4 weeks after treatment to evaluate left ventricular (LV) ejection fraction (EF). We used echocardiography to assess dogs’ LV diastolic function.
Results: There was no difference of LVEF between these 2 groups at post-MI 2 weeks (DS-1 treated dogs vs. vehicle-treated dogs: 55.0 ± 6.3 % vs. 52.9 ± 1.6 %, p = 0.61). Compared to controls at 4 weeks post infusion, the DS-1 treated dogs had preserved LVEF (DS-1 treated dogs vs. vehicle-treated dogs: 54.2 ± 1.2 % vs. 47.6 ± 2.3 %, p = 0.01). The DS-1 treated group had better LV diastolic function (DS-1 treated dogs vs. vehicle-treated dogs: 15.2 ± 1.2 vs. 23.0 ± 1.0, p < 0.001 for left atrial volume index; 7.3 ± 1.2 vs. 14.6 ± 1.3, p = 0.002 for mitral E/e′). Although there was no significant difference of arteriole density and fibrotic/infarct size between these 2 groups, however the DS-1 treated animals had an increased amount of uniform collagen orientation, indicating that there was more parallel alignment of the collagen fibers in the treated dogs which may result in improved diastolic dysfunction.
Conclusions: Our study demonstrated a therapeutic benefit of intravenously infusing DS-1 cells at subacute MI period. However, further research is still warranted to determine the precise mechanism responsible for this therapeutic benefit.
Poster Hall, Hall C
Friday, March 17, 2017, 10:00 a.m.-10:45 a.m.
Session Title: Interventional Cardiology: Translation and Pre-Clinical Research
Abstract Category: 25. Interventional Cardiology: Translation and Pre-clinical Research
Presentation Number: 1116-195
- 2017 American College of Cardiology Foundation