ABSTRACT
Systemic arterial hypertension (SAH), a clinical syndrome characterized by persistent elevation of arterial pressure, is often associated with abnormalities such as microvascular rarefaction, defective angiogenesis, and endothelial dysfunction. Mesenchymal stem cells (MSCs), which normally induce angiogenesis and improve endothelial function, are defective in SAH. The central aim of this study was to evaluate whether priming of MSCs with endothelial growth medium (EGM-2) increases their therapeutic effects in spontaneously hypertensive rats (SHRs). Adult female SHRs were administered an intraperitoneal injection of vehicle solution (n = 10), MSCs cultured in conventional medium (DMEM plus 10% FBS, n = 11), or MSCs cultured in conventional medium followed by 72 hours in EGM-2 (pMSC, n = 10). Priming of the MSCs reduced the basal cell death rate in vitro. The administration of pMSCs significantly induced a prolonged reduction (10 days) in arterial pressure, a decrease in cardiac hypertrophy, an improvement in endothelium-dependent vasodilation response to acetylcholine, and an increase in skeletal muscle microvascular density compared to the vehicle and MSC groups. The transplanted cells were rarely found in the hearts and kidneys. Taken together, our findings indicate that priming of MSCs boosts stem cell therapy for the treatment of SAH.
ABSTRACT
Chagas disease is an endemic parasitic disease, caused by the flagellate protozoan Trypanosoma cruzi, with a high prevalence in Latin America. During its chronic phase, chronic chagasic cardiomyopathy is the most apparent clinical form, affecting 25-30% of patients. This clinical form may present as congestive heart failure, thromboembolic phenomena, cardiac arrhythmias and sudden death. Pathological findings in the heart include mononuclear inflammatory infiltrate, focal myocarditis, epicarditis and neuroganglionitis, associated with variable focal fibrosis and widely variable autonomic dysfunction. The immune-inflammatory response has been considered to be the cause of the autonomic dysfunction, which may trigger life-threatening arrhythmias and sudden death. In the last few years, several reports in the literature have described the marked role played by the autonomic nervous system in the modulation of the immune-inflammatory response in some experimental models of infectious, ischaemic and autoimmune diseases. However, nothing is known about this autonomic neural modulation of the immune response in Chagas disease. In the present report, we discuss several sets of evidence suggesting that changes in the autonomic drive directed towards the heart could modify blood and tissue parasitism, as well as inflammatory infiltration, in chagasic cardiomyopathy. The pathogenic implications of these potential neural immune manipulations are also discussed.
