title: Differentiated mesenchymal stem cells ameliorate cardiovascular complications in diabetic rats.
abstract: Cardiovascular manifestations are one of the major complications of type 1 diabetes mellitus (T1DM) and supersede the slow progression of DM in most cases as the leading cause of mortality. There have been many studies and trials in regenerating the functional β-cells of islets from mesenchymal stem cells (MSCs) with varied success. The effect of MSCs ex vivo differentiated to mimic functional insulin-secreting β-cells of islets and their impact on restoration of diabetic complications and transplantation via systemic delivery have not been well studied. In the current study, bone marrow MSCs differentiated to insulin-secreting β-cells are used to treat STZ-induced diabetic rats. The post-homing effects of the differentiated MSCs (dMSCs) were endogenous with definite reversal of diabetic parameters. Consequently, the altered cardiac functions like heart beat rate, left ventricular performance, contractility index and physiological body weight gain due to hyperglycemia were amelorated into normacy. The primary onset cardiac perfomance and the endothelial activation were well evidenced by high fibrinogen levels and systolic blood pressure (SBP) being reversed on the treatment by dMSCs. Further high basal [Ca(2+)]c in isolated endothelial cells and thereby increased ROS confirmed the endothelial activation. The levels of pro-apoptotic makers p53 and Bax were highly expressed in the diabetic groups indicating oxidative stress through ROS induced by high cytosolic calcium skewing the cells towards apoptosis. The expression of the anti-apoptotic marker Bcl-2 was observed to be low in the diabetic group further augmenting the stress state of endothelial cells (ECs) in T1DM. Restoration of [Ca(2+)]c chelates ROS and the subsequent reversal of pro- and anti-apoptotic markers after the successful treatment of dMSCs proved that endogenous reconstitution of insulin secretion improves diabetic-induced cardiac manifestations.
authors.affiliation: Department of Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia.|Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Haidara
authors.affiliation: Center for Stem Cell Research, College of Medicine, King Khalid University, Abha, Saudi Arabia.|Department of Cardiology, College of Medicine, King Khalid University, Abha, Saudi Arabia.
authors.forename: Abdullah S
authors.initials: AS
authors.lastname: Assiri
authors.affiliation: Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Youssef
authors.affiliation: Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Manal M
authors.initials: MM
authors.lastname: Mahmoud
authors.affiliation: Department of Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia.
authors.forename: Eajaz
authors.initials: E
authors.lastname: Ahmed M S
authors.affiliation: Center for Stem Cell Research, College of Medicine, King Khalid University, Abha, Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al-Hakami
authors.affiliation: Center for Stem Cell Research, College of Medicine, King Khalid University, Abha, Saudi Arabia. ccharishjabali@gmail.com.|Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia. ccharishjabali@gmail.com.
authors.forename: Harish C
authors.initials: HC
authors.lastname: Chandramoorthy
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000150:complications* / Q000628:therapy*; D002454:Cell Differentiation; D019070:Cell Lineage; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000628:therapy*; D042783:Endothelial Cells / Q000378:metabolism; D004727:Endothelium / Q000473:pathology; D006706:Homeostasis; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000166:cytology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007328:Insulin; D017382:Reactive Oxygen Species; D002118:Calcium