Circulating miRNAs as Potential Biomarkers Associated with Cardiac Remodeling and Fibrosis in Chagas Disease Cardiomyopathy.

Chagas disease (CD) affects approximately 6-7 million people worldwide, from which 30% develop chronic Chagas cardiomyopathy (CCC), usually after being asymptomatic for years. Currently available diagnostic methods are capable of adequately identifying infected patients, but do not provide information regarding the individual risk of developing the most severe form of the disease. The identification of biomarkers that predict the progression from asymptomatic or indeterminate form to CCC, may guide early implementation of pharmacological therapy. Here, six circulating microRNAs (miR-19a-3p, miR-21-5p, miR-29b-3p, miR-30a-5p, miR-199b-5p and miR-208a-3p) were evaluated and compared among patients with CCC (n = 28), CD indeterminate form (n = 10) and healthy controls (n = 10). MiR-19a-3p, miR-21-5p, and miR-29b-3p were differentially expressed in CCC patients when compared to indeterminate form, showing a positive correlation with cardiac dysfunction, functional class, and fibrosis, and a negative correlation with ejection fraction and left ventricular strain. Cardiac tissue analysis confirmed increased expression of microRNAs in CCC patients. In vitro studies using human cells indicated the involvement of these microRNAs in the processes of cardiac hypertrophy and fibrosis. Our study suggests that miRNAs are involved in the process of cardiac fibrosis and remodeling presented in CD and indicate a group of miRNAs as potential biomarkers of disease progression in CCC.

Image-guided percutaneous intralesional administration of mesenchymal stromal cells in subjects with chronic complete spinal cord injury: a pilot study.

BACKGROUND AIMS: The potential of cell therapies to improve neurological function in subjects with spinal cord injury (SCI) is currently under investigation. In this context, the choice of cell type, dose, route and administration regimen are key factors. Mesenchymal stromal cells (MSCs) can be easily obtained, expanded and are suitable for autologous transplantation. Here we conducted a pilot study that evaluated safety, feasibility and potential efficacy of intralesional MSCs transplantation performed through image-guided percutaneous injection, in subjects with chronic complete SCI. METHODS: Five subjects with chronic traumatic SCI (>6 months), at thoracic level, classified as American Spinal Cord Injury Association impairment scale (AIS) grade A, complete injury, were included. Somatosensory evoked potentials (SSEP), spinal magnetic resonance imaging (MRI) and urodynamics were assessed before and after treatment. Autologous MSCs were injected directly into the lesion site through percutaneous injection guided by computerized tomography (CT). RESULTS: Tomography-guided percutaneous cell transplantation was a safe procedure without adverse effects. All subjects displayed improvements in spinal cord independence measure (SCIM) scores and functional independence measure (FIM), mainly due to improvements in bowel movements and regularity. Three subjects showed improved sensitivity to tactile stimulation. Two subjects improved AIS grade to B, incomplete injury, although this was sustained in only one of them during the study follow-up. CONCLUSION: Autologous bone marrow MSC transplantation, performed through CT-guided percutaneous injection, was shown to be safe and feasible. Further studies are required to demonstrate efficacy of this therapeutic scheme.