Acute aerobic exercise increases exogenously infused bone marrow cell retention in the heart

Abstract

Stem cell therapy for myocardial infarction (MI) has been shown to improve cardiac function and reduce infarct size. Exercise training, in the form of cardiac rehabilitation, is an essential part of patient care post-MI. Hence, we tested the effects of acute and chronic aerobic exercise on stem cell retention and cardiac remodeling post-MI. Small epicardial MI’s were induced in 12-month-old C57BL/6 mice via cryoinjury. Two weeks post-MI, vehicle infusion (N = 4) or GFP+ bone marrow-derived cells (BMC) were injected (tail vein I.V.) immediately after acute exercise (N = 14) or sedentary conditions (N = 14). A subset of mice continued a 5-week intervention of chronic treadmill exercise (10–13 m/min; 45 min/day; 4 days/week; N = 7) or remained sedentary (N = 6). Exercise tolerance was assessed using a graded exercise test, and cardiac function was assessed with echocardiography. Acute exercise increased GFP+ BMC retention in the infarcted zone of the heart by 30% versus sedentary (P < 0.05). This was not associated with alterations in myocardial function or gene expression of key cell adhesion molecules. Animals treated with chronic exercise increased exercise capacity (P < 0.05) and cardiac mass (P < 0.05) without change in left ventricular ejection fraction (LVEF), infarct size, or regional wall thickness (P = NS) compared with sedentary. While BMC’s alone did not affect exercise capacity, they increased LVEF (P < 0.05) and Ki67+ nuclei number in the border zone of the heart (P < 0.05), which was potentiated with chronic exercise training (P < 0.05). We conclude that acute exercise increases BMC retention in infarcted hearts and chronic training increases exogenous BMC-mediated effects on stimulating the cardiomyocyte cell cycle. These preclinical results suggest that exercise may help to optimize stem cell therapeutics following MI.

Evaluation of Multiple Biological Therapies for Ischemic Cardiac Disease

“…The use of cell- and gene-based therapeutics to preserve cardiac function and prevent tissue loss post-MI has made considerable advancements over the past several years 13,49–52 . Many cells types and genes have been proposed as therapeutic options including adult-derived cells, such as skeletal myoblasts 53,54 , fetal stem cells 55,56 , pluripotent stem cells 57,58 , and BM-MSCs 13,58 . In recent years, stem cells derived from various areas of umbilical cord tissue have also been studied and characterized 59–62 .…”

Myocardial apoptosis and mesenchymal stem cells with acute exercise

“…A separate study by our group demonstrated that exercise can increase retention of bone marrow mononucleated cells in the myocardium (Chirico et al. ). Thus, we also performed a PCR array for extracellular matrix and cell adhesion molecules.…”

Resistance Exercise Increases the Regulation of Skeletal Muscle FSTL1 Consequently Improving Cardiac Angiogenesis in Rats with Myocardial Infarctions

“…The protective effect of exercise on MI had been demonstrated by many evidences [6,23,46,47]. However, the pathways and mechanisms of the protective effects on heart mediated by exercise remain largely unknown.…”