A comparative study of mesenchymal stem cell transplantation with its paracrine effect on control of hyperglycemia in type 1 diabetic rats

被引：20
作者：
Aali E. [1 ]
Mirzamohammadi S. [1 ]
Ghaznavi H. [1 ]
Madjd Z. [4 ]
Larijani B. [3 ]
Rayegan S. [1 ]
Sharifi A.M. [1 ,2 ,3 ]
机构：
[1] Razi Drug Research Center, Department of Pharmacology, Iran University of Medical Sciences, Tehran
[2] Department of Tissue Engineering and Cell Therapy, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran
[3] Endocrine and Metabolism Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran
[4] Oncopathology Research Center, Department of Pathology, Iran University of Medical Sciences, Tehran
来源：
Journal of Diabetes & Metabolic Disorders | / 13卷 / 1期
关键词：
Diabetes mellitus; Hyperglycemia; Mesenchymal stem cells;
D O I：
10.1186/2251-6581-13-76
中图分类号：
学科分类号：
摘要：
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.Conclusion: 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. © 2014 Aali et al.; licensee BioMed Central Ltd.
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  • [1] Bottazzo G.F., Florin-Christensen A., Doniach D., Islet- cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies, Lancet, 2, pp. 1279-1283, (1974)
  • [2] Shapiro A.M., Lakey J.R., Ryan E.A., Korbutt G.S., Toth E., Warnock G.L., Kneteman N.M., Rajotte R.V., Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen, N Engl J Med, 343, 4, pp. 230-238, (2000)
  • [3] Balamurugan AN B.R., Giannoukakis N., Prospective and challenges of islet transplantation for the therapy of autoimmune diabetes, Pancreas, 32, 3, pp. 231-243, (2006)
  • [4] Dominique Farge L.V., Mesenchymal stem cell-Stem cell therapy for tyoe 1 diabetes, Proc Rom Acad, 1, pp. 59-70, (2008)
  • [5] Montanya E., Islet- and stem-cell-based tissue engineering in diabetes, Curr Opin Biotechnol, 15, pp. 435-440, (2004)
  • [6] Abraham E.J., Leech C.A., Lin J.C., Zulewski H., Habener J.F., Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulinproducing cells, Endocrinology, 143, pp. 3152-3161, (2002)
  • [7] Schmied B.M., Ulrich A., Matsuzaki H., Ding X., Ricordi C., Weide L., Moyer M.P., Batra S.K., Adrian T.E., Pour P.M., Transdifferentiation of human islet cells in a long-term culture, Pancreas, 23, pp. 157-171, (2001)
  • [8] Bonner-Weir S., Taneja M., Weir G.C., Tatarkiewicz K., Song K.H., Sharma A., O'Neil J.J., In vitro cultivation of human islets from expanded ductal tissue, Proc Natl Acad Sci U S A, 97, pp. 7999-8004, (2000)
  • [9] Wagner J., Kean T., Young R., Dennis J.E., Caplan A.I., Optimizing mesenchymal stem cell-based therapeutics, Curr Opin Biotechnol, 20, pp. 531-536, (2009)
  • [10] Li G., Zhang X.A., Wang H., Wang X., Meng C.L., Chan C.Y., Yew D.T., Tsang K.S., Li K., Tsai S.N., Ngai S.M., Han Z.C., Lin M.C., He M.L., Kung H.F., Comparative proteomic analysis of mesenchymal stem cells derived from human bone marrow, umbilical cord, and placenta: implication in the migration, Proteomics, 9, pp. 20-30, (2009)
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