Acute myocardial infarction is a major problem of world public health and available treatments have limited efficacy. Cardiac cell therapy is a new therapeutic strategy focused on regeneration and repair of the injured cardiac muscle. Among different cell types used, mesenchymal stem cells (MSC) have been widely tested in preclinical studies and several clinical trials have evaluated their clinical efficacy in myocardial infarction. However, the beneficial effects of MSC in humans are limited due to poor engraftment and survival of these cells, therefore ways to overcome these obstacles should improve efficacy. Different strategies have been used, such as genetically modifying MSC, or preconditioning the cells with factors that potentiate their survival and therapeutic mechanisms. In this review we compile the most relevant approaches used to improve MSC therapeutic capacity and to understand the molecular mechanisms involved in MSC mediated cardiac repair.

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González AM, Garcia T, Samper E, Rickmann M, Vaquero EC, Molero X. Assessment of the protective effects of oral tocotrienols in arginine chronic-like pancreatitis. Am J Physiol Gastrointest Liver Physiol 301: G846 -G855, 2011. First published August 18, 2011 doi:10.1152/ajpgi.00485.2010.-Tocotrienols exhibit anti-inflammatory properties over macrophages and promote cytotoxicity in activated pancreatic stellate cells, suggesting that they may limit chronic pancreatitis progression. We aimed to quantitate the effect of oral tocotrienols on a rat model of chronic pancreatic injury. Chroniclike pancreatitis was induced by repeated arginine pancreatitis. Palm oil tocotrienol-rich fraction (TRF) was given by gavage before and after pancreatitis inductions. Amylase and hydroxyproline were determined in pancreatic homogenates; collagen, fibronectin, ␣-smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), and phosphorylated Smad3 were assessed by Western blotting. Transforming growth factor (TGF)-␤1 was measured in plasma. Morphological assessment included light microscopy, fibrosis area fraction, and collagen network fractal analysis. Arginine pancreatitis induced pancreatic atrophy and increased hydroxyproline that ameliorated after TRF. Arginine increased TGF-␤1 (185 Ϯ 40 vs. 15 Ϯ 2 ng/ml; P Ͻ0.01) that was blunted by TRF (53 Ϯ 19; P Ͻ 0.01). TRF reduced protease and Smad3 activation, collagen, and fibronectin. ␣-SMA increased and GFAP diminished in arginine pancreatitis, consistent with long-term stellate cell activation, and TRF reverted these changes to basal. Arginine pancreatitis increased fibrosis area fraction (4.5 Ϯ 0.3% vs. 0.2 Ϯ 0.2%), collagen network complexity (fractal dimension 1.52 Ϯ 0.03 vs. 1.42 Ϯ 0.01; P Ͻ 0.001), and inhomogeneity (lacunarity 0.63 Ϯ 0.03 vs. 0.40 Ϯ 0.02; P Ͻ 0.001), which were all reduced by TRF (1.3 Ϯ 0.4%, 1.43 Ϯ 0.02%, and 0.51 Ϯ 0.03%, respectively; P Ͻ 0.01). Best correlation coefficients were obtained when comparing fibrosis area fraction with lacunarity (r ϭ 0.88) and both parameters with pancreatic weight (r ϭ Ϫ0.91 and Ϫ0

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