title: A comparative study of mesenchymal stem cell transplantation with its paracrine effect on control of hyperglycemia in type 1 diabetic rats.
abstract: BACKGROUND
  Many studies suggested mesenchymal stem cells (MSCs) transplantation as a new approach to control hyperglycemia in type 1 diabetes mellitus through differentiation mechanism. In contrary others believed that therapeutic properties of MSCs is depends on paracrine mechanisms even if they were not engrafted. This study aimed to compare these two approaches in control of hyperglycemia in STZ-induced diabetic rats.
  
  
  METHODS
  Animals were divided into five groups: normal; diabetic control; diabetic received MSCs; diabetic received supernatant of MSCs; diabetic received co-administration of MSCs with supernatant. Blood glucose, insulin levels and body weight of animals were monitored during experiment. Immunohistochemical and immunofluorescence analysis were performed to monitor functionality and migration of labeled-MSCs to pancreas.
  
  
  RESULTS
  First administration of MSCs within the first 3 weeks could not reduce blood glucose, but second administration significantly reduced blood glucose after week four compared to diabetic controls. Daily injection of supernatant could not reduce blood glucose as efficient as MSCs. Interestingly; Co-administration of MSCs with supernatant significantly reduced blood glucose more than other treated groups. Insulin levels and body weight were significantly increased in MSCs + supernatant-treated animals compared to other groups. Immunohistological analysis showed an increase in number and size of islets per section respectively in supernatant, MSCs and MSCs + supernatant-treated groups.
  
  
  CONCLUSIONS
  Present study exhibited that repeated-injection of MSCs reduced blood glucose and increased serum insulin levels in recipient rats. Injection of supernatant could not reverse hyperglycemia as efficient as MSCs. Interestingly; co-administration of MSCs with supernatant could reverse hyperglycemia more than either group alone.
authors: Razi Drug Research Center and Department of Pharmacology, Iran University of Medical Sciences, Tehran, Iran.
authors: Ehsan
authors: E
authors: Aali
authors: Razi Drug Research Center and Department of Pharmacology, Iran University of Medical Sciences, Tehran, Iran.
authors: Solmaz
authors: S
authors: Mirzamohammadi
authors: Razi Drug Research Center and Department of Pharmacology, Iran University of Medical Sciences, Tehran, Iran.
authors: Habib
authors: H
authors: Ghaznavi
authors: Oncopathology Research Center and Department of Pathology, Iran University of Medical Sciences, Tehran, Iran.
authors: Zahra
authors: Z
authors: Madjd
authors: Endocrine and Metabolism Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors: Bagher
authors: B
authors: Larijani
authors: Razi Drug Research Center and Department of Pharmacology, Iran University of Medical Sciences, Tehran, Iran.
authors: Samira
authors: S
authors: Rayegan
authors: Razi Drug Research Center and Department of Pharmacology, Iran University of Medical Sciences, Tehran, Iran ; Department of Tissue Engineering and Cell Therapy, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran ; Endocrine and Metabolism Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors: Ali M
authors: AM
authors: Sharifi
keywords: Diabetes mellitus; Hyperglycemia; Mesenchymal stem cells