Posts Tagged: 473728-58-4

Background The liver has the remarkable capacity to regenerate in order

Background The liver has the remarkable capacity to regenerate in order to compensate for lost or damaged hepatic tissue. impaired liver regeneration. Methods C57BL/6 mice were fed with a regular diet (normal mice) or with a high-fat diet (obese mice) to induce HS. After 30?weeks of diet exposure, 70% hepatectomy (Hpx) was performed and normal and obese mice were divided into two groups that received 5??105 MSCs or vehicle via the tail vein immediately after Hpx. Results We confirmed a significant inhibition of hepatic regeneration when liver steatosis was present, while the hepatic regenerative response was promoted by infusion of MSCs. Specifically, MSC administration improved the hepatocyte proliferative response, PCNA-labeling index, DNA synthesis, liver function, and also reduced the number of apoptotic hepatocytes. These effects may be associated to the paracrine secretion of trophic factors by MSCs and the hepatic upregulation 473728-58-4 of key cytokines and growth factors relevant for cell proliferation, which ultimately improves the survival rate of the mice. Conclusions MSCs represent a promising therapeutic strategy to improve liver regeneration in patients with HS as well as for increasing the number of donor organs available for transplantation. Electronic supplementary material The online version of this article (doi:10.1186/s13287-016-0469-y) contains supplementary material, which is available to authorized users. test was 473728-58-4 used to compare mean values between two groups. p?Rabbit Polyclonal to HTR2B 7?days post-Hpx (which was the day time when the mice were sacrificed). Fig. 1 MSC administration raises survival rate and enhances liver regeneration of obese mice after 70% hepatectomy. Survival rate of mice and liver regeneration were evaluated in all experimental organizations up to 7?days post-surgery. a Kaplan-Meier survival … Body excess weight modifications following Hpx were monitored as a marker of health fitness (Fig.?1b). Mice in the obese?+?Vh group showed a higher excess weight loss than mice in the normal?+?Vh group, however MSC administration significantly reduced these changes in both experimental organizations. Number?1c shows liver regeneration rates in the four organizations of mice, 2 and 7?days post-Hpx, expressed while percentage of liver mass regeneration. In normal organizations, no variations were observed in the regenerated liver mass at both time points evaluated, self-employed of MSC administration. Two days post-Hpx, the rate of liver mass regeneration was lower in the obese?+?Vh group, compared to the normal group, however, MSC administration increased the rates up to normal group levels. MSC administration induces hepatocyte expansion and reduces apoptotic rate after 70% hepatectomy To determine the hepatic proliferative activity, immunofluorescence staining for the expansion marker PCNA was performed 2?days post-Hpx. As demonstrated in Fig.?2a and ?andc,c, significantly more PCNA (+) nuclei were observed in the MSC-treated versus vehicle-treated group, irrespective if the mice were normal or obese. Fig. 2 MSC administration enhances expansion and inhibits apoptosis of liver parenchymal cells after 70% hepatectomy. Cellular expansion and apoptosis were analyzed pre- and 2?days post liver resection in all experimental organizations. The effect of … To further confirm the expansion of hepatocytes, we analyzed DNA synthesis by BrdU staining. In accordance with the earlier results, the percentage of BrDu 473728-58-4 (+) nuclei was higher in the MSC-treated organizations (Fig.?2b, m). Earlier reports possess shown that 2?days after Hpx, hepatocytes are the principal proliferating cells [26, 34, 42], however, the identity of the proliferating cells was confirmed by a two times immunofluorescence for albumin and BrDu incorporation (Additional file 473728-58-4 4). It offers been reported that hepatocyte death happens if the cells are unable to total the mitotic cycle. TUNEL assay was used to address whether apoptosis contributes.