Dataset Information

Intervention for early diabetic nephropathy by mesenchymal stem cells in a preclinical nonhuman primate model.

ABSTRACT:

Background

Diabetic nephropathy (DN) is one of the most severe chronic diabetic complications and the main cause of end-stage renal disease. Chronic inflammation plays a key role in the development of DN. However, few treatment strategies are available; therefore, new and effective strategies to ameliorate DN at the early stage must be identified.

Methods

Mesenchymal stem cells (MSCs) are characterized by anti-inflammatory and immune regulatory abilities. We developed a rhesus macaque model of DN and administered MSCs four times over 2?months. We measured blood glucose level, HbA1c, and levels of renal function parameters in the blood and urine, and cytokine levels in the kidney and blood circulatory system of rhesus macaques. Also, we analyzed the renal pathological changes of rhesus macaques. In vitro, we treated tubular epithelial cells (HK2) with 30?mmol/L glucose and 10?ng/mL human recombinant TNF-alpha (rhTNF-?) and explored the effects of MSCs on inflammation and Na⁺-glucose cotransporter 2 (SGLT2) expression in HK2.

Results

We found that MSCs decreased the blood glucose level and daily insulin requirement of DN rhesus macaques. Furthermore, MSCs had a dominant function in improving renal function and decreasing SGLT2 expression on renal tubular epithelial cells. Also, renal pathological changes were ameliorated after MSC treatment. Moreover, MSCs powerfully reduced inflammation, especially decreased the level of pro-inflammatory cytokine interleukin-16 (IL-16), in the kidney and blood circulatory system.

Conclusions

Our study is an important step to explore the mechanism of MSCs in ameliorating the early stage of DN, potentially through influencing SGLT2 expression and resulting in improved glycemic control and anti-inflammation. We hope these findings would provide insights for the clinical application of MSCs in DN.

SUBMITTER: An X

PROVIDER: S-EPMC6889652 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

Intervention for early diabetic nephropathy by mesenchymal stem cells in a preclinical nonhuman primate model.

An Xingxing X Liao Guangneng G Chen Younan Y Luo Ai A Liu Jingping J Yuan Yujia Y Li Lan L Yang Lichuan L Wang Hong H Liu Fang F Yang Guang G Yi Shounan S Li Yuanmin Y Cheng Jingqiu J Lu Yanrong Y

Stem cell research & therapy 20191202 1

<h4>Background</h4>Diabetic nephropathy (DN) is one of the most severe chronic diabetic complications and the main cause of end-stage renal disease. Chronic inflammation plays a key role in the development of DN. However, few treatment strategies are available; therefore, new and effective strategies to ameliorate DN at the early stage must be identified.<h4>Methods</h4>Mesenchymal stem cells (MSCs) are characterized by anti-inflammatory and immune regulatory abilities. We developed a rhesus mac ...[more]

PMID: 31791397

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Dataset Information

Intervention for early diabetic nephropathy by mesenchymal stem cells in a preclinical nonhuman primate model.

Background

Methods

Results

Conclusions

Publications

Intervention for early diabetic nephropathy by mesenchymal stem cells in a preclinical nonhuman primate model.

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