Systemic administration of multipotent mesenchymal stromal cells reverts hyperglycemia and prevents nephropathy in type 1 diabetic mice

Biol Blood Marrow Transplant. 2008 Jun;14(6):631-40. doi: 10.1016/j.bbmt.2008.01.006. Epub 2008 Apr 14.


Multipotent mesenchymal stromal cells (MSCs), often labeled mesenchymal stem cells, contribute to tissue regeneration in injured bone and cartilage, as well as in the infarcted heart, brain, and kidney. We hypothesize that MSCs might also contribute to pancreas and kidney regeneration in diabetic individuals. Therefore, in streptozotocin (STZ)-induced type 1 diabetes C57BL/6 mice, we tested whether a single intravenous dose of MSCs led to recovery of pancreatic and renal function and structure. When hyperglycemia, glycosuria, massive beta-pancreatic islets destruction, and mild albuminuria were evident (but still without renal histopathologic changes), mice were randomly separated in 2 groups: 1 received 0.5 x 10(6) MSCs that have been ex vivo expanded (and characterized according to their mesenchymal differentiation potential), and the other group received the vehicle. Within a week, only MSC-treated diabetic mice exhibited significant reduction in their blood glucose levels, reaching nearly euglycemic values a month later. Reversion of hyperglycemia and glycosuria remained for 2 months at least. An increase in morphologically normal beta-pancreatic islets was observed only in MSC-treated diabetic mice. Furthermore, in those animals albuminuria was reduced and glomeruli were histologically normal. On the other side, untreated diabetic mice presented glomerular hyalinosis and mesangial expansion. Thus, MSC administration resulted in beta-pancreatic islets regeneration and prevented renal damage in diabetic animals. Our preclinical results suggest bone marrow-derived MSC transplantation as a cell therapy strategy to treat type 1 diabetes and prevent diabetic nephropathy, its main complication.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Albuminuria / etiology
  • Albuminuria / prevention & control
  • Animals
  • Cell Differentiation / drug effects
  • Cells, Cultured / cytology
  • Cells, Cultured / drug effects
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / surgery*
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / prevention & control*
  • Glomerular Mesangium / pathology
  • Hyperglycemia / etiology
  • Hyperglycemia / prevention & control*
  • Infusions, Intravenous
  • Islets of Langerhans / pathology
  • Islets of Langerhans / physiology
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / physiology
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology
  • Mice
  • Mice, Inbred C57BL
  • Multipotent Stem Cells / transplantation*
  • Osteocytes / cytology
  • Random Allocation
  • Regeneration
  • Stromal Cells / transplantation