1.Cardioprotective Effects of Wharton Jelly Derived Mesenchymal Stem Cell Transplantation in a Rodent Model of Myocardial Injury.
Taghrid GAAFAR ; Wael ATTIA ; Shereen MAHMOUD ; Dina SABRY ; Osama Abdel AZIZ ; Dina RASHEED ; Hala HAMZA
International Journal of Stem Cells 2017;10(1):48-59
BACKGROUND: Whartons jelly-derived mesenchymal stem cells are a valuable alternative source that possess multipotent properties, easy to obtain and available in large scale compared to BMMSCs. We investigated the possibility of cardiac function improvement post isoproterenol induced cardiac injury in a rat model following human WJMSCs transplantation. MATERIALS AND METHODS: MSCs were extracted and cultured from cord WJ, characterized by morphology, Immunophenotyping and differentiation to osteoblast and adipocytes. WJMSCs were labeled with PKH2 linker dye. Wistar rats were divided into control group, ISO group (injected with 2 doses of isoproterenol) to induce myocardial injury and ISO group transplanted with labelled WJMSCs. ECG, electrocardiographic patterns, cardiac marker enzymes, tracing of labeled MSCs and immunohistochemical analysis of myocardial cryosections were studied. RESULTS AND CONCLUSIONS: WJ derived MSCs were expanded for more than 14 passages while maintaining their un-differentiated state, were positive for MSC markers and were able to differentiate into adipocyte and osteoblast. We demonstrated that intravenously administered WJMSCs were capable of homing predominently in the ischemic myocardium. Cardiac markers were positively altered in stem cell treated group compared to ISO group. ECG and ECHO changes were improved with higher survival rate. WJMSCs could differentiate into cardiac-like cells (positive for cardiac specific proteins) in vivo. WJMSCs infusion promoted cardiac protection and reduced mortality, emphasizing a promising therapeutic role for myocardial insufficiency.
Adipocytes
;
Electrocardiography
;
Humans
;
Immunophenotyping
;
Isoproterenol
;
Mesenchymal Stem Cell Transplantation*
;
Mesenchymal Stromal Cells*
;
Models, Animal
;
Mortality
;
Myocardium
;
Osteoblasts
;
Rats, Wistar
;
Rodentia*
;
Stem Cells
;
Survival Rate
;
Transplantation
;
Wharton Jelly*
2.Cardamonin exerts a protective effect against autophagy and apoptosis in the testicles of diabetic male rats through the expression of Nrf2 via p62-mediated Keap-1 degradation
Shereen M. SAMIR ; Mahmoud ELALFY ; Eman Mohamad El NASHAR ; Mansour A. ALGHAMDI ; Eman HAMZA ; Mohamed Saad SERRIA ; Mona G. ELHADIDY
The Korean Journal of Physiology and Pharmacology 2021;25(4):341-354
Cardamonin (CARD) is a chalconoid with anti-inflammatory and antioxidant properties, and it is present in several plants. We sought to explore whether CARD exerts any positive effects against hyperglycemia-induced testicular dysfunction caused by type 2 diabetes and aimed to identify its possible intracellular pathways. Adult male rats were subdivided into six groups: control, CARD, diabetic (DM), DM + glibenclamide (GLIB), DM + CARD and DM + GLIB + CARD. Type 2 DM induced a significant increase in blood glucose and insulin resistance, along with diminished serum insulin, testosterone and gonadotropins levels, which were associated with the impairment of key testicular androgenic enzymes and cellular redox balance. Administration of CARD at a dose of 80 mg/kg for 4 weeks effectively normalized all of these alterations, and the improvement was confirmed by epididymal sperm analysis. After treatment with CARD, the pathological changes in spermatogenic tubules were markedly improved. Significantly, CARD upregulated testicular glucose transporter-8 (GLUT-8) expression and had inhibitory effects on elevated autophagy markers and caspase-3 immunoreactive cells. Furthermore, our results revealed that CARD was able to attenuate damage via activation of Nrf2 through the p62-dependent degradation of testicular anti-Kelch-like ECH-associated protein-1 (Keap-1). In conclusion, this study suggests that CARD provides protection against diabetic stress-mediated testicular damage. The use of CARD with conventional anti-diabetic therapy was associated with improved efficacy compared with conventional therapy alone.
3.Cardamonin exerts a protective effect against autophagy and apoptosis in the testicles of diabetic male rats through the expression of Nrf2 via p62-mediated Keap-1 degradation
Shereen M. SAMIR ; Mahmoud ELALFY ; Eman Mohamad El NASHAR ; Mansour A. ALGHAMDI ; Eman HAMZA ; Mohamed Saad SERRIA ; Mona G. ELHADIDY
The Korean Journal of Physiology and Pharmacology 2021;25(4):341-354
Cardamonin (CARD) is a chalconoid with anti-inflammatory and antioxidant properties, and it is present in several plants. We sought to explore whether CARD exerts any positive effects against hyperglycemia-induced testicular dysfunction caused by type 2 diabetes and aimed to identify its possible intracellular pathways. Adult male rats were subdivided into six groups: control, CARD, diabetic (DM), DM + glibenclamide (GLIB), DM + CARD and DM + GLIB + CARD. Type 2 DM induced a significant increase in blood glucose and insulin resistance, along with diminished serum insulin, testosterone and gonadotropins levels, which were associated with the impairment of key testicular androgenic enzymes and cellular redox balance. Administration of CARD at a dose of 80 mg/kg for 4 weeks effectively normalized all of these alterations, and the improvement was confirmed by epididymal sperm analysis. After treatment with CARD, the pathological changes in spermatogenic tubules were markedly improved. Significantly, CARD upregulated testicular glucose transporter-8 (GLUT-8) expression and had inhibitory effects on elevated autophagy markers and caspase-3 immunoreactive cells. Furthermore, our results revealed that CARD was able to attenuate damage via activation of Nrf2 through the p62-dependent degradation of testicular anti-Kelch-like ECH-associated protein-1 (Keap-1). In conclusion, this study suggests that CARD provides protection against diabetic stress-mediated testicular damage. The use of CARD with conventional anti-diabetic therapy was associated with improved efficacy compared with conventional therapy alone.