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

Jong Hee Park; Inah Hwang; Soo Han Hwang; Hoon Han; Hunjoo Ha

doi:10.1016/j.diabres.2012.09.034

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

Jong Hee Park, Inah Hwang, Soo Han Hwang, Hoon Han, Hunjoo Ha

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

90 Scopus citations

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
Pages (from-to)	465-473
Number of pages	9
Journal	Diabetes Research and Clinical Practice
Volume	98
Issue number	3
DOIs	https://doi.org/10.1016/j.diabres.2012.09.034
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.diabres.2012.09.034

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

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.",

keywords = "Diabetic nephropathy, Fibrosis, Mesenchymal stem cells, Transforming growth factor-β1",

author = "Park, {Jong Hee} and Inah Hwang and Hwang, {Soo Han} and Hoon Han and Hunjoo Ha",

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.",

year = "2012",

month = dec,

doi = "10.1016/j.diabres.2012.09.034",

language = "English",

volume = "98",

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journal = "Diabetes Research and Clinical Practice",

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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

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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 -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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