The Effect of Different Routes of Injection of Bone Marrow Mesenchymal Stem Cells on Parotid Glands of Rats Receiving Cisplatin: A Comparative Study

BACKGROUND AND OBJECTIVES: Cisplatin is a powerful antitumor chemotherapeutic agent that is widely used in the treatment of many cancers but it has many side effects on many organs including salivary glands. Bone marrow is considered to be a rich environment that comprises many types of stem cells of which BMSCs (Bone marrow mesenchymal stem cells) are the most studied with potentiality to differentiate into many cell types. This study was conducted to evaluate the effect of different routes of injection of BMSCs on parotid glands of rats receiving cisplatin. METHODS AND RESULTS: Sprague-Dawley rats were divided into 3 groups: a negative control group receiving phosphate buffered saline, a positive control group receiving cisplatin, and an experimental group where rats received cisplatin and then received iron oxide-labeled BMSCs by either intravenous or intraparotid routes or both. Animals were sacrificed at periods of 3,6,10 and 15 days after cisplatin injection, then histological, ultrastructural and immunohistochemical studies were done. The experimental stem cell treated group showed better histological features and increased PCNA proliferation index when compared to the control. The systemic and combination groups showed better results than the local group. Iron oxide-labeled cells were detected with Prussian blue stain. CONCLUSIONS: This study proved that BMSCs can improve cisplatin induced cytotoxicity in parotid glands. Systemic administration showed to have a better effect than local intraparotid administration and comparable effect to combined administration.

common mutation in methylene tetrahydrofolate reductase gene, inflammation and atherosclerosis in chronic renal failure

Accelerated atherosclerosis is the major cause of mortality in patients on chronic haemodialysis [HD]. Inflammation and endothelial activation or dysfunction might be the major factors leading to high cardiovascular mortality rate in HD patients. Also, C667T mutation of methyltetrahydrofolate reductase [MTHFR] might be associated with accelerated athcrosclerosis. The present study was designed to clarify the role of inflammation, endothelial activation or dysfunction and genotyping of MTHFR enzyme which affect the level or homocysteine and their relation to carotid artery intima-media thickness [CIMT] as an indicator of atherosclerosis. Forty four [44] chronic haemodialysis [HD] patients and 40 healthy subjects were included in the study. Serum highly sensitive C reactive protein [hs-CRP] and IL-6 were measured as inflammatory markers, soluble vascular cell adhesion molecule-1 [sVCAM-1] was measured as a marker of endothelial activation and dysfunction. Common carotid intimal media thickness [CC-IMT] was assessed by carotid artery ultrasonography. genotyping of MTHFR enzyme which affect the level of homocysteine was analyzed by PCR RFLIP technique. Chronic HD patients had elevated levels of inflammatory markers [hs-CRP and IL-6], enhanced endothelial activation or dysfunction demonstrated by elevated VCAM-1 as compared by healthy controls. Haemodialysis patients had significantly higher CC-IMT levels. There is a significant positive correlation between inflammatory cytokines [hs-CRP and IL-6], and each with VCAM-1 and CC-IMT There is no difference in the genotype of C667T MTHFR found between patients and controls, but this mutation especially the TT genotype is associated with development of atherosclerosis as indicated by the increase of CC-IMT