Abstract
BACKGROUND: Bone marrow stem cells (BMSCs) may be a novel treatment modality for organ ischemia, possibly through beneficial paracrine mechanisms. However, stem cells from older hosts exhibit decreased function during stress. We therefore hypothesized that (1) BMSCs derived from neonatal hosts would provide protection to ischemic myocardium, and (2) neonatal stem cells would enhance postischemic myocardial recovery above that seen with adult stem cell therapy. MATERIALS AND METHODS: Female adult Sprague Dawley rat hearts were subjected to an ischemia/reperfusion protocol via Langendorff isolated heart preparation (15 min equilibration, 25 min ischemia, and 60 min reperfusion). BMSCs were harvested from adult and neonatal mice and cultured through several passages under normal conditions (37 degrees C, 5% CO(2)/air). Immediately prior to ischemia, 1 million adult or neonatal BMSCs were infused into the coronary circulation. Cardiac functional parameters were continuously recorded. RESULTS: Pretreatment with adult BMSCs significantly increased postischemic myocardial recovery as noted by improved left ventricular developed pressure, end diastolic pressure, contractility, and rate of relaxation. Neonatal stem cells, however, did not cause any noticeable improvement in myocardial functional parameters following ischemia. CONCLUSION: Neonatal and adult BMSCs are distinctly different in the degree of beneficial tissue protection that they can provide. The data herein suggests that a critical age exists as to when stem cells become fully activated to provide their beneficial protective properties. Defining the genes that initiate these protective properties may allow for genetic amplification of beneficial signals, and the generation of "super stem cells" that provide maximum protection to ischemic tissues.