Autologous Transplantation of Adipose-Derived Mesenchymal Stem Cells Markedly Reduced Acute Ischemia-Reperfusion Lung Injury in a Rodent Model

Abstract

BackgroundThis study tested the hypothesis that autologous transplantation of adipose-derived mesenchymal stem cells (ADMSCs) can effectively attenuate acute pulmonary ischemia-reperfusion (IR) injury.MethodsAdult male Sprague-Dawley (SD) rats (n = 24) were equally randomized into group 1 (sham control), group 2 (IR plus culture medium only), and group 3 (IR plus intravenous transplantation of 1.5 × 106 autologous ADMSCs at 1h, 6h, and 24h following IR injury). The duration of ischemia was 30 minutes, followed by 72 hours of reperfusion prior to sacrificing the animals. Blood samples were collected and lungs were harvested for analysis.ResultsBlood gas analysis showed that oxygen saturation (%) was remarkably lower, whereas right ventricular systolic pressure was notably higher in group 2 than in group 3 (all p < 0.03). Histological scoring of lung parenchymal damage was notably higher in group 2 than in group 3 (all p < 0.001). Real time-PCR demonstrated remarkably higher expressions of oxidative stress, as well as inflammatory and apoptotic biomarkers in group 2 compared with group 3 (all p < 0.005). Western blot showed that vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, oxidative stress, tumor necrosis factor-α and nuclear factor-κB were remarkably higher, whereas NAD(P)H quinone oxidoreductase 1 and heme oxygenase-1 activities were lower in group 2 compared to those in group 3 (all p < 0.004). Immunofluorescent staining demonstrated notably higher number of CD68+ cells, but significantly fewer CD31+ and vWF+ cells in group 2 than in group 3.ConclusionADMSC therapy minimized lung damage after IR injury in a rodent model through suppressing oxidative stress and inflammatory reaction.

Autologous transplantation of adipose-derived mesenchymal stem cells attenuates cerebral ischemia and reperfusion injury through suppressing apoptosis and inducible nitric oxide synthase

“…Nonetheless, all these changes were significantly reversed by intravenous administration of ADMSCs. Our data are consistent with several recent reports showing that restoration of the levels of some apoptotic markers, such as caspase-3, Bax and Bcl-2, play an essential role in the protective effects of ADMSCs therapy against I/R injury (12,13). Altogether, our findings not only corroborated previous reports that apoptosis produces neuronal death after I/R injury, but also provided evidence that ADMSCs implantation is able to prevent the apoptosis of neurons.…”

“…In contrast, adipose-derived MSCs (ADMSCs) have several distinct advantages of being abundant, easy to obtain with minimal invasiveness, and readily cultured to a sufficient number for autologous transplantation without the ethical issues of allografting (10). Recently, a growing body of experimental evidence has demonstrated the effectiveness of ADMSC-based therapy in improving end-organ ischemia or I/R injury (11)(12)(13). However, the possibility that autologous transplantation of ADMSCs may have a neuroprotective effect on cerebral I/R injury has not yet been examined.…”

Adipose-Derived Stem Cells in Tissue Regeneration: A Review

“…In support of this, Chen et al 2011, using a model of kidney IR treated using direct injection of ASCs, find increased clearance of creatinine and urea from blood plasma, together with higher levels of the antioxidant markers NAD(P)H quinine oxidoreductase, heme-oxygenase 1/HO-1, glutathione peroxidase, and glutathione reductase [314]. Increased antioxidant marker levels versus controls (i.e., NAD(P)H quinine oxidoreductase and HO-1) have also been reported, together with decreased hepatic oxidative stress upon multiple injections of ASCs in hepatic IR models [312]. In vivo, GFP-labelled ASCs can improve the vasculature in excisional wounds in normal and diabetic rats and are found to coexpress CD31, suggesting their endothelial differentiation [315].…”

“…Transendocardial injections of ASCs in a minipig model of IR injury results in long-lasting improvements in cardiac function, along with increased angiogenesis and vasculogenesis [311]. Higher numbers of CD31+ve and vWF+ve cells have also been found in models of lung IR following ASC injection, suggesting increased vessel formation [312]. Amelioration of kidney IR injury can be achieved using ASCs [313].…”

Mesenchymal Stromal Cells in Transplantation Rejection and Tolerance

“…Importantly, MSCs express CD59, a complement regulatory protein, and also release complement factor H that protects them from complement lysis (Tu et al 2010;Moll et al 2011). In addition, stimulation through C3aR and C5aR protect MSCs from oxidative damage (Schraufstatter et al 2009) and MSCs produce a number of antioxidants including hemeoxygenase-1 and superoxide dismutase (Kemp et al 2010;Mougiakakos et al 2011), and have been shown to suppress oxidative stress and inflammation in ischemia reperfusion injury models in vivo (Chen et al 2011Sun et al 2011;Du et al 2012). The exact mechanisms of action are unclear; however, MSC protection in these models was associated with increased expression of IL-10, heme oxygenase-1 (HO-1), and hepatocyte growth factor, decreased expression of the proinflammatory cytokines IL-1b, TNF-a, and interferon g (IFN-g), reduced reactive oxygen species, reduced apoptosis and decreased numbers of activated T cells, and infiltrating immune cells (Hara et al 2011;Sun et al 2011;Chen et al 2012;Du et al 2012).…”