Comparative Study on Bone Marrow-Versus Adipose-Derived Stem Cells on Regeneration and Re-Innervation of Skeletal Muscle Injury in Wistar Rats.

BACKGROUND: Skeletal muscle injuries are frequent clinical challenges due to associated fibrosis and disability. Regenerative medicine is an emerging promising strategy for such cases. The aim of this study was to compare between the effects of bone marrow-mesenchymal stem cells (BM-MSCs) versus adipose tissue stromal cells (ADSCs) on regeneration and re-innervation of skeletal muscle laceration injury in Wistar rats at different time intervals. METHODS: Six young male rats were used as a source of allogenic MSCs. Eighty-four adult female rats were divided into: Group I (control), Group II (Untreated Laceration): right gluteal muscle was lacerated and left for spontaneous healing, Group III (BM-MSCs): right gluteal muscle was lacerated with concomitant local intramuscular injection of 1 × 106 BM-MSCs in the lacerated muscle, Group IV (ADSCs): right gluteal muscle was lacerated with concomitant local intramuscular injection of 1 × 106 ADSCs in lacerated muscle. Rats were sacrificed after one, two and eight weeks. Muscles were processed to prepare sections stained with H&E, Mallory's trichrome and immune-histochemical staining (neurofilament light chain). RESULTS: A significant increase in collagen fibers and failure of re-innervation were noticed in untreated laceration group. BM-MSCs-treated groups showed regeneration of muscle fibers but with increased collagen fibers. Meanwhile, ADSCs showed better regenerative effects evidenced by significant increase in the number of myotubes and significant decrease in collagen deposition. Re-innervation was noticed in MSCs-injected muscles after 8 weeks of laceration. CONCLUSION: Both BM-MSCs and ADSCs improved regeneration of skeletal muscle laceration injury at short- and long-term durations. However, fibrosis was less in ADSCs-treated rats. Effective re-innervation of injured muscles occurred only at the long-term duration.

Insights into hepatic and renal FXR/DDAH-1/eNOS pathway and its role in the potential benefit of rosuvastatin and silymarin in hepatic nephropathy.

OBJECTIVES: The repression of renal Farnesoid X Receptor (FXR) had been shown to result from lack of bile acid production from cirrhotic liver. We hypothesized that silymarin and rosuvastatin (Rvs) could have a hepatorenal therapeutic effects in hepatic nephropathy through induction of FXR. METHODS: Forty two male Wistar rats were used; naïve (n = 12); six of them were sacrificed after 4 weeks and six continued till the end of the experiment. Thirty rats were treated as follows: Rvs, silymarin, thioacetamide (TAA), TAA + Rvs and TAA + silymarin. Liver and kidney function tests as well as the renal and hepatic expression of transforming growth factor ß1 (TGFß1), FXR, dimethylarginine dimethylaminohydrolase-1 (DDAH-1) and eNOS were performed. Histological and immuno-histochemical studies of liver and kidney were also done. RESULTS: TAA-inducted liver cirrhosis was associated with significant deterioration of liver and renal functions together with increasing expression of hepatic and renal TGFß1 and decreasing expression of hepatic and renal FXR, DDAH-1 and eNOS. Giving silymarin or Rvs induced hepatic and renal improvement which was evidenced biochemically and histologically. Significant positive correlation was detected between all the investigated biomarkers except for the correlation between FXR and TGFß1 which was negative. CONCLUSIONS: In conclusion, liver cirrhosis is associated with deterioration of renal functions. Silymarin and Rvs have a potential hepatorenal therapeutic benefit through simultaneous enhancement of FXR/DDAH-1/eNOS pathway in both organs.

The protective effect of pentoxifylline versus silymarin on the pancreas through increasing adenosine by CD39 in a rat model of liver cirrhosis: Pharmacological, biochemical and histological study.

Impaired glucose homoeostasis due to insulin resistance and decrease sensitivity of pancreatic ß-cells is a feature of liver disease and results into hepatogenous diabetes. Decrease expression of CD39 was linked to inflammation and occurrence of diabetes. Therefore, we performed this study to explore the protective effect of pentoxifylline (PTX) and silymarin administration on the ß-cells of the pancreas in a rat model of thioacetamide induced liver cirrhosis. Biochemical, histological and immunohistochemistry studies of the liver and pancreas were performed and provided an evidence on the protective effect of PTX to pancreatic ß-cells compared to silymarin. Also, silymarin induced a significant improvement of liver cirrhosis compared to PTX. In conclusion, the potential protective effect of PTX against ß-cells deterioration could be attributed to increasing pancreatic CD39 expression and the subsequent increase of adenosine.