SUMMARYBackground: Mesenchymal stem cells (MSCs) have immense self-renewal capability. They can be differentiated into many cell types and therefore hold great potential in the field of regenerative medicine. MSCs can be converted into beating cardiomyocytes by treating them with DNA-demethylating agents. Some of these compounds are nucleoside analogs that are widely used for studying the role of DNA methylation in biological processes as well as for the clinical treatment of leukemia and other carcinomas. Aims: To achieve a better therapeutic option for cardiovascular regeneration, this study was carried out using MSCs treated with two synthetic compounds, zebularine and 5-azacytidine. It can be expected that treated MSCs prior to transplantation may increase the likelihood of successful regeneration of damaged myocardium. Methods: The optimized concentrations of these compounds were added separately into the culture medium and the treated cells were analyzed for the expression of cardiac-specific genes by RT-PCR and cardiac-specific proteins by immunocytochemistry and flow cytometry. Treated MSCs were cocultured with cardiomyocytes to see the fusion capability of these cells. Results: mRNA and protein expressions of GATA4, Nkx2.5, and cardiac troponin T were observed in the treated MSCs. Coculture studies of MSCs and cardiomyocytes have shown improved fusion with zebularine-treated MSCs as compared to untreated and 5-azacytidine-treated MSCs. Conclusion: The study is expected to put forth another valuable aspect of certain compounds, that is, induction of transdifferentiation of MSCs into cardiomyocytes. This would serve as a tool for modified cellular therapy and may increase the probability of better myocardial regeneration.
The current study demonstrates that CGPA is the only significant predictor, indicating that Optimism tends to be higher for students with a higher CPGA. None of the other independent variables (age, year of study, gender) showed a significant relationship.
Our findings showed that pharmacological activation of Epac-Rap1 improves cardiac function through better survival, adhesion and differentiation of transplanted cells. Transplantation of these MSCs in the infarct area restored functional myocardium.
IntroductionAbdominal injuries are responsible for 10% of the mortalities due to trauma. Delays in early diagnosis or misdiagnoses are two major reasons for the mortality and morbidity associated with abdominal trauma. The objectives of this study were to determine the frequency of visceral injuries in patients with abdominal trauma and compare the frequency of visceral injuries in patients with blunt and penetrating abdominal trauma.MethodsWe conducted a cross-sectional study from May 2016 to May 2018 of patients presenting to the emergency department (ED) at Jinnah Postgraduate Medical Center in Karachi, Pakistan. Patients were 12 to 65 years old and presented within 24 hours of abdominal trauma. We recorded the type of abdominal visceral injuries, such as liver, spleen, intestine, stomach, mesentery, and pancreas.ResultsThe mean patient age was 31 ±13 years. Penetrating trauma was found in most patients (n=72, 51%). Liver injuries were found in 37 patients (26.4%), spleen injuries in 29 patient (20.7%), stomach injuries in eight patients (5.7%), intestine injuries in 67 patients (47.9%), mesentery injuries in 21 patients (15%), and pancreas injuries in nine patients (6.4%). The type of abdominal trauma was found significantly associated with liver injury (p-value 0.021), and intestine injury (p-value <0.001).ConclusionPenetrating trauma (51.4%) was more common than blunt trauma (48.5%), and intestines are the most commonly affected by penetrating and blunt trauma injuries (70.1% and 47.8%, respectively). The liver is the most commonly affected (42.85%) in blunt trauma injuries, followed by the spleen (28.5%). The appropriate authorities should consider this information when instituting public health and safety initiatives.
Summary
Aims
Mesenchymal stem cells (MSCs) hold significant promise as potential therapeutic candidates following cardiac injury. However, to ensure survival of transplanted cells in ischemic environment, it is beneficial to precondition them with growth factors that play important role in cell survival and proliferation. Aim of this study is to use interleukin‐7 (IL‐7), a cell survival growth factor, to enhance the potential of rat bone marrow MSCs in terms of cell fusion in vitro and cardiac function in vivo.
Methods
Mesenchymal stem cells were transfected with IL‐7 gene through retroviral vector. Normal and transfected MSCs were co‐cultured with neonatal cardiomyocytes (CMs) and cell fusion was analyzed by flow cytometry and fluorescence microscopy. These MSCs were also transplanted in rat model of myocardial infarction (MI) and changes at tissue level and cardiac function were assessed by histological analysis and echocardiography, respectively.
Results
Co‐culture of IL‐7 transfected MSCs and CMs showed significantly higher (P < 0.01) number of fused cells as compared to normal MSCs. Histological analysis of hearts transplanted with IL‐7 transfected MSCs showed significant reduction (P < 0.001) in infarct size and better preservation (P < 0.001) of left ventricular wall thickness as compared to normal MSCs. Presence of cardiac‐specific proteins, α‐actinin, and troponin‐T showed that the transplanted MSCs were differentiated into cardiomyocytes. Echocardiographic recordings of the experimental group transplanted with transfected MSCs showed significant increase in the ejection fraction and fractional shortening (P < 0.01), and decrease in diastolic and systolic left ventricular internal diameters (P < 0.001) and end systolic and diastolic volumes (P < 0.01 and P < 0.001, respectively).
Conclusion
Interleukin‐7 is able to enhance the fusogenic properties of MSCs and improve cardiac function. This improvement may be attributed to the supportive action of IL‐7 on cell proliferation and cell survival contributing to the regeneration of damaged myocardium.
This study was aimed to enhance the healing potential of rat bone marrow mesenchymal stem cells against chronic diabetic wounds through interleukin-7 (IL-7) transfection. IL-7 plays an important role in wound healing and acts as a survival factor in some cell types. This study involves isolation, propagation, and characterization of mesenchymal stem cells (MSCs) and their modification with IL-7 gene via retroviral transfection. Transfected MSCs were assessed for their effect on angiogenic genes by qPCR. Wound healing potential of transfected MSCs was analyzed by scratch assay in vitro and by transplanting these cells in rat diabetic wound models in vivo. Wound area was measured for a period of 15 days and subsequent histological analysis was performed. qPCR results showed increased expression of IL-7 gene (p ≤ 0.05) and also principal angiogenic genes, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), VEGF receptor 1 (FLT-1), and VEGF receptor 2 (FLK-1) (p ≤ 0.05). Neuropilin-1 (NRP-1) did not show any significant change. In vitro analysis of IL-7 MSCs showed intense cell-cell connections and tube formation as compared to the normal MSCs. Rate of wound closure was more (p ≤ 0.001) in case of diabetic group transplanted with IL-7 MSCs. Histological examination revealed enhanced vascular supply in skin tissues of diabetic animals transplanted with IL-7 transfected MSCs as compared to normal MSCs. Immunohistochemical results showed significantly higher expression of IL-7 (p ≤ 0.001) and α-smooth muscle actin(p ≤ 0.001) in the tissue sections of IL-7 transfected group as compared to normal MSCs and the diabetic control group; the latter indicates increase in the number of blood vessels. It is concluded from this study that IL-7 overexpression in MSCs can enhance the healing potential of MSCs and aid in wound closure in diabetic animals through the induction of angiogenic genes.
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