Betania Souza Monteiro

Treatment of critical defects produced in calvaria of mice with mesenchymal stem cells

Mesenchymal stem cells (MSC) are present in specialized niches in perivascular regions of adult tissues and are able to differentiate into various cell types, such as those committed to repairing. Bone marrow derived MSC from eight young mice C57BL/ 6 gfp(+) were expanded in culture for repairing critical defects in calvarial bone produced in twenty-four young isogenic adult C57BL/6 mice. The animals were subjected to a cranial defect of 6.0mm diameter and divided into two equal experimental groups. Control group did not receive any treatment and the treated group received a MSC pellet containing 1.0 x 10(7) cells/mL into the defects. The group treated with MSC showed increased angiogenesis and amount of new bone deposited on the defect limits than that observed in the control group. The results demonstrated that transplantation of bone marrow-derived MSC of C57BL/6 gfp(+) mice to bone critical defects produced in mice calvarial contributes positively to the bone repair process. MSC presets ability to influence the correct functioning of osteoblasts, increases the amount of mobilized cells for the repairing process, speeds up growth, and increases deposition of bone matrix.

Mesenchymal stem cell therapy associated with endurance exercise training: Effects on the structural and functional remodeling of infarcted rat hearts.

We tested the effects of early mesenchymal stem cell (MSC) therapy associated with endurance exercise on the structural and functional cardiac remodeling of rats with myocardial infarctation (MI). Male Wistar rats (40 days old) were divided into 6 groups: control and exercise sham; control and exercise MI; and control and exercise MI MSC. MI was surgically induced and bone marrow-derived MSCs were immediately injected via caudal vein (concentration: 1 × 10(6 )cells). Twenty-four hours later ET groups exercised on a treadmill (5 days/week; 60 min/day; 60% of maximal running velocity) for 12 weeks. Structural and functional changes were determined by echocardiography. Contractility and intracellular global calcium ([Ca(2 +)]i) transient were measured in myocytes from the left ventricular (LV) non-infarcted area. Calcium regulatory proteins were measured by Western blot. MI increased (p < 0.05) heart, ventricular and LV weights and its ratios to body weight; LV internal dimension in diastole (LVID-D) and in systole (LVID-S) and LV free wall in diastole (LVFW-D), but reduced the thickness of interventricular septum in systole (IVS-S), ejection fraction (EF) and fractional shortening (FS). MI augmented (p < 0.05) the times to peak and to half relaxation of cell shortening as well as the amplitude of the [Ca(2 +)]i transient and the times to peak and to half decay. Early MSCs therapy restored LVFW-D, IVS-S and the amplitude and time to half decay of the [Ca(2 +)]i transient. Early endurance exercise intervention increased (p < 0.05) LVFW-S, IVS-S, EF and FS, and reduced the times to peak and to half relaxation of cell shortening, and the amplitude of the [Ca(2 +)]i transient. Exercise training also increased the expression of left ventricular SERCA2a and PLBser16. Nevertheless, the combination of these therapies did not cause additive effects. In conclusion, combining early MSCs therapy and endurance exercise does not potentiate the benefits of such treatments to structural and functional cardiac remodeling in infarcted rats.

Acute and chronic observations of complete atrioventricular block in rats

The mechanisms of production, and gross, microscopic and electrocardiograhic findings of surgically-induced complete heart block (CHB) in the adult rat are presented. This is an effective in vivo model for establishing alternative methods to electronic pacemakers and for providing detailed information aimed at replacement, reduction and refinement of the technique. Sternal thoracotomy was employed to identify the epicardial fat pad by the aortic root, used as a landmark for cauterization of the atrioventricular (AV) node. Stable CHB was produced in 60 rats with a 70% survival rate. The best survival rate was observed in 8-week-old animals weighing 221 ± 27.6 g. Heart rate before cauterization was 387 ± 55 bpm, reduced after cauterization to 126 ± 40 bpm in the survival and to 65 ± 19 bpm in the non-survival groups. At 30 days findings were: elevated left ventricular end-diastolic pressure (21 ± 5.4 mmHg, P < 0.05); maximal rate of rise of left ventricular pressure (LVP) during isovolumetric contraction (2192 ± 235 mmHg/s, P < 0.05); maximal rate of decrease of LVP (−1658 ± 191 mmHg/s, P < 0.05); isovolumetric relaxation constant (5.7 ± 0.8 ms, P < 0.05) with wet-to-dry lung–weight ratio (78.1 ± 0.4, P < 0.05); heart weight/body weight (0.6 ± 0.1, P < 0.05); heart volume (1.8 ± 0.3 mL, P < 0.05); longitudinal diameter (20.2 ± 1.91 mm, P < 0.05); and transversal diameter (17.0 ± 1.4 mm, P < 0.05) with supported dilated cardiomyopathy which culminated in chronic heart failure. CHB hearts had increased preload and replacement of myofibrils by collagen. CHB was achieved reproducibly by cauterization of the rat AV node and/or His bundle. This led to electrophysiological, hemodynamic, and structural remodeling, and could be useful in long-term cardiac remodeling assessments and potential therapy development.