MSC: Mechanism of Action

Immunomodulation and paracrine functions make MSCs to be the eligible candidate for allogeneic transplantation. In this regard, MSCs home specifically to injured tissue and exert their immunomodulatory activity with the secretion of vascular endothelial growth factor (Guan et al. 2013), antiapoptotic (Bcl-2) (Zhen et al.

2008), and anti-inflammatory factors (Guan et al. 2013; Rojas et al. 2005; Shigemura et al. 2006; Gupta et al. 2007; Nemeth et al. 2009) thus stimulating angiogenesis, promoting host cell recovery, and repairing the injured tissue. Exogenously administered MSCs modulate the function of host cells within the injury by cell contact- dependent and paracrine mechanisms and by the transfer of cellular materials via microvesicles (Islam et al. 2012; Zhu et al. 2014). Preclinical studies using MSCs provide promising results for lung disorders, including emphysema (Guan et al. 2013; Zhen et al. 2010), BPD (Chang et al. 2011; van Haaften et al. 2009), fibrosis (Cargnoni et al. 2009; Moodley et al. 2009), and acute RDS (Gupta et al. 2007; Nemeth et al. 2009; Mei et al. 2010). However, development of stem cell therapy for pulmonary diseases remains a major challenge. Further, understanding of lung stem cell fate during disease may prove to be of critical importance for drug intervention and autologous therapies. Niches for resident MSC have been identified in many adult tissues and more recently in the lungs (Martin et al. 2008). Lung regeneration involves activation of progenitor cells as well as cell replacement through proliferation of remaining undamaged cells. The pathways and factors that control this process and its role in disease are only now being explored.

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