Human umbilical cord blood-derived mesenchymal stem cells prevent diabetic renal injury through paracrine action

Diabetes Res Clin Pract. 2012 Dec;98(3):465-73. doi: 10.1016/j.diabres.2012.09.034. Epub 2012 Sep 29.

Abstract

Aims: The present study examined renoprotective effect of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) in diabetes. NRK-52E cells were utilized to determine the paracrine effect of hUCB-MSC.

Methods: hUCB was harvested with the mother's consent. MSC obtained from the hUCB were injected through the tail vein. Growth arrested and synchronized NRK-52E cells were stimulated with transforming growth factor-β1 (TGF-β1) in the presence of hUCB-MSC conditioned media.

Results: At 4 weeks after the streptozotocin (STZ) injection, diabetic rats showed significantly increased urinary protein excretion, renal and glomerular hypertrophy, fractional mesangial area, renal expression of TGF-β1 and α-smooth muscle actin, and collagen accumulation but decreased renal E-cadherin and bone morphogenic protein-7 expression, confirming diabetic renal injury. hUCB-MSC effectively prevented diabetic renal injury except renal and glomerular hypertrophy without a significant effect on blood glucose. CM-DiI-labeled hUCB-MSC and immunostaining of PKcs, a human nuclei antigen, confirmed a few engraftment of hUCB-MSC in diabetic kidneys. hUCB-MSC conditioned media inhibited TGF-β1-induced extracellular matrix upregulation and epithelial-to-mesenchymal transition in NRK-52E cells in a concentration-dependent manner.

Conclusions: These results demonstrate the renoprotective effect of hUCB-MSC in STZ-induced diabetic rats possibly through secretion of humoral factors and suggest hUCB-MSC as a possible treatment modality for diabetic renal injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Separation
  • Cells, Cultured
  • Cord Blood Stem Cell Transplantation*
  • Cytokines / metabolism
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy*
  • Diabetic Nephropathies / prevention & control*
  • Epithelial-Mesenchymal Transition*
  • Extracellular Matrix / metabolism
  • Fetal Blood / cytology
  • Graft Survival
  • Humans
  • Hypertrophy
  • Kidney / metabolism
  • Kidney / pathology*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Paracrine Communication*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Cytokines
  • Recombinant Proteins
  • TGFB1 protein, human
  • Transforming Growth Factor beta1