Adult mesenchymal stem cells and the NO pathways.

Skeletal Research Center, Department of Biology, Case Western Reserve University, Cleveland, OH 44106.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 02/2013; DOI: 10.1073/pnas.1221406110
Source: PubMed
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    ABSTRACT: Significance: Bronchopulmonary dysplasia (BPD) is a disease of the developing lung that afflicts extreme preterm infants in the neonatal intensive care unit (NICU). Follow-up studies into adulthood show that BPD isn't merely a problem of the neonatal period, as it also may predispose to early-onset emphysema and poor lung function in later life. Recent advances: The increasing promise of bone marrow or umbilical cord derived-mesenchymal stromal cells (MSCs) to repair neonatal and adult lung diseases, may for the first time offer the chance to make substantial strides in improving the outcome of extreme premature infants at risk of developing BPD. As more knowledge has been obtained on MSCs over the last decades, it has become clear that each organ has its own reservoir of endogenous MSCs, including the lung. Critical issues: We have only barely scratched the surface on what resident lung MSCs exactly are and what their role and function in lung development may be. Moreover, what happens to these putative repair cells in BPD when alveolar development goes awry and why do their counterparts from the bone marrow and umbilical cord succeed in restoring normal alveolar development when they themselves do not? Future directions: Much work remains to be done to validate lung MSCs, but with the high potential of MSC-based treatment for BPD and other lung diseases, a thorough understanding of the endogenous lung MSC will be pivotal to get to the bottom of these diseases.
    Antioxidants & Redox Signaling 12/2013; · 8.20 Impact Factor
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    ABSTRACT: To evaluate the potential therapeutic effect of the infusion of hMSCs for the correction of liver injuries, we performed total body radiation exposure of NOD/SCID mice. After irradiation, mir-27b level decreases in liver, increasing the directional migration of hMSCs by upregulating SDF1 α . A significant increase in plasmatic transaminases levels, apoptosis process in the liver vascular system, and in oxidative stress were observed. hMSC injection induced a decrease in transaminases levels and oxidative stress, a disappearance of apoptotic cells, and an increase in Nrf2, SOD gene expression, which might reduce ROS production in the injured liver. Engrafted hMSCs expressed cytokeratin CK18 and CK19 and AFP genes indicating possible hepatocyte differentiation. The presence of hMSCs expressing VEGF and Ang-1 in the perivascular region, associated with an increased expression of VEGFr1, r2 in the liver, can confer a role of secreting cells to hMSCs in order to maintain the endothelial function. To explain the benefits to the liver of hMSC engraftment, we find that hMSCs secreted NGF, HGF, and anti-inflammatory molecules IL-10, IL1-RA contributing to prevention of apoptosis, increasing cell proliferation in the liver which might correct liver dysfunction. MSCs are potent candidates to repair and protect healthy tissues against radiation damages.
    BioMed research international. 01/2013; 2013:151679.
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    ABSTRACT: The endodontic management of permanent immature teeth is fraught with challenges. Although treatment modalities for vital pulp therapy in these teeth provide long-term favorable outcome, the outcomes from the treatment of pulp necrosis and apical periodontitis are significantly less predictable. Immature teeth diagnosed with pulp necrosis have been traditionally treated with apexification or apexogenesis approaches. Unfortunately, these treatments provide little to no benefit in promoting continued root development. Regenerative endodontic procedures have emerged as an important alternative in treating teeth with otherwise questionable long-term prognosis because of thin, fragile dentinal walls and a lack of immunocompetency. These procedures rely heavily on root canal chemical disinfection of the root canal system. Traditionally, irrigants and medicaments have been chosen for their maximum antimicrobial effect without consideration for their effects on stem cells and the dentinal microenvironment. Translational research has been crucial to provide evidence for treatment modifications that aim to increase favorable outcome while steering away from common pitfalls in the currently used protocols. In this review, recent advances learned from translational research related to disinfection in regenerative endodontics are presented and discussed.
    Journal of endodontics 04/2014; 40(4):S52–S57. · 2.95 Impact Factor