Human mesenchymal stem cells provide protection against radiation-induced liver injury by antioxidative process, vasculature protection, hepatocyte differentiation and trophic effects

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 . 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.

Mesenchymal stem cells – A new hope for radiotherapy-induced tissue damage?

“…Infusion into mice after liver irradiation has been shown to result in a significant decrease of radiation-induced liver damage as assessed by liver function tests and quantification of apoptotic hepatocytes [49,50]. However, the exact mechanisms have been subject to some controversy: In one mouse model, no measurable numbers of MSCs could be detected in the irradiated liver tissue, and the beneficial effects of MSC-based treatment of liver damage were attributed to the cells' paracrine and immunomodulatory functions [49,51].…”

Plant Extracts and Plant-Derived Compounds: Promising Players in Countermeasure Strategy Against Radiological Exposure: A Review

“…Adding to its advantage is also the easy availability of the plants, which are consumed in one form or the other across the globe. As shown in Table 1 DOI:http://dx.doi.org/10.7314/APJCP.2014.15.6.2405 radicals are known to be generated in vivo because of radiation exposure (Parihar et al, 2007;Swarts et al, 2007;Sharan et al, 2011;Peebles et al, 2012;Francois et al, 2013;Mikhailenko et al, 2013), and hence scavenging them can protect the cells or tissue from oxidative injury. At the same time, some of the plants/plant-derived compounds also induce the biological antioxidant defence system such as SOD, GSH, CAT and GPx to counter the radiological effects in experimental animals in order to prevent cell/tissue injury.…”

“…has been known to cause different types of effects in biological systems ranging from oxidative damages caused by ionization products, free radicals, and reactive oxygen species (ROS) to damages to DNA and its interaction with macromolecules such as proteins (Chen et al, 2007;Swarts et al, 2007;Sharma et al, 2008;2009;Shuryak and Brenner, 2010;Cramers et al, 2011;Ramachandran and Nair, 2011;Sharan et al, 2011;Mukherjee et al, 2012;Barg et al, 2013;Francois et al, 2013). The interactions of these agents with cells has been shown to cause alterations in the gene expression pattern, mutations, weakening of repair mechanisms (Little, 2000;Sharma et al, 2009;Cramers et al, 2011;Mukherjee et al, 2012;Francois et al, 2013;Mikhailenko et al, 2013).…”

“…The interactions of these agents with cells has been shown to cause alterations in the gene expression pattern, mutations, weakening of repair mechanisms (Little, 2000;Sharma et al, 2009;Cramers et al, 2011;Mukherjee et al, 2012;Francois et al, 2013;Mikhailenko et al, 2013). Agents that can be radioprotective must counter some or all the damaging effects of radiological exposure in the cell including those mentioned above.…”

Umbilical Cord MSCs Reverse D-Galactose-Induced Hepatic Mitochondrial Dysfunction <i>via</i> Activation of Nrf2/HO-1 Pathway

“…5,6) In addition, compelling evidence suggest that MSCs is a potential antioxidative candidate and exerts its hepatoprotective effects by redox-signaling pathways. 7,8) However, the underlying mechanism is not fully elucidated. Previous studies have shown that D-galactose (D-Gal) overload can mimic hepatic failure in clinical settings, 9,10) and the mechanisms are associated with accumulation of free radicals, antioxidant defensive ability impairment and mitochondrial dysfunction.…”