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.
Original language | English |
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Pages (from-to) | 465-473 |
Number of pages | 9 |
Journal | Diabetes Research and Clinical Practice |
Volume | 98 |
Issue number | 3 |
DOIs | |
State | Published - Dec 2012 |
Bibliographical note
Funding Information:This work was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare (A090289), National Research Foundation (2012R1A2A1A03006092), and Ewha Global Top5 Grant 2011 of Ewha Womans University, Republic of Korea.
Keywords
- Diabetic nephropathy
- Fibrosis
- Mesenchymal stem cells
- Transforming growth factor-β1