TY - JOUR
T1 - Human umbilical cord blood-derived mesenchymal stem cells prevent diabetic renal injury through paracrine action
AU - Park, Jong Hee
AU - Hwang, Inah
AU - Hwang, Soo Han
AU - Han, Hoon
AU - Ha, Hunjoo
N1 - 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.
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
KW - Diabetic nephropathy
KW - Fibrosis
KW - Mesenchymal stem cells
KW - Transforming growth factor-β1
UR - http://www.scopus.com/inward/record.url?scp=84870673962&partnerID=8YFLogxK
U2 - 10.1016/j.diabres.2012.09.034
DO - 10.1016/j.diabres.2012.09.034
M3 - Article
C2 - 23026513
AN - SCOPUS:84870673962
SN - 0168-8227
VL - 98
SP - 465
EP - 473
JO - Diabetes Research and Clinical Practice
JF - Diabetes Research and Clinical Practice
IS - 3
ER -
