Valsartan- and melatonin-supported adipose-derived mesenchymal stem cells preserve renal function in chronic kidney disease rat through upregulation of prion protein participated in promoting PI3K-Akt-mTOR signaling and cell proliferation

Bone marrow mesenchymal stem cells (BMSCs) can be used to treat bone defects. The neuropeptide substance P (SP) plays an important role in a variety of life activities. However, the effect of SP on BMSCs differentiation in high glucose environment remains unclear. Rat BMSCs were isolated and divided into control group; high glucose group; and SP group. The secretion of SP was detected by ELISA; cell proliferation was detected by MTT assay; apoptosis activity was detected by Cas-pase3 activity kit. Real time PCR was performed to measure Bax and Bcl-2 expression. Alizarin red staining was to detect calcified nodule formation. Western blot was done to measure AMPK/mTOR signaling protein expression. In high glucose environment, SP secretion was significantly decreased, along with increased cell proliferation, Caspase3 activity and Bax expression. Meanwhile, Bcl-2 expression, ALP activity and calcified nodules formation was significantly decreased with reduced AMPK phosphorylation and increased mTOR expression (P < 0.05). SP addition in high glucose environment significantly promoted SP secretion and cell proliferation, decreased Caspase3 activity and Bax expression, increased Bcl-2 expression, ALP activity and calcification nodules formation with increased AMPK phosphorylation and decreased mTOR expression (P < 0.05). In high glucose environment, SP secretion is decreased in BMSCs. Up-regulation of SP in BMSCs cells in high glucose environment inhibit the apoptosis of BMSCs and promote cell proliferation and osteogenesis by regulating AMPK/mTOR signaling pathway.

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Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice

Kidney International ◽

10.1038/sj.ki.5001521 ◽

2006 ◽

Vol 70 (1) ◽

pp. 121-129 ◽

Cited By ~ 196

Author(s):

V. Ninichuk ◽

O. Gross ◽

S. Segerer ◽

R. Hoffmann ◽

E. Radomska ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Kidney Disease ◽

Interstitial Fibrosis ◽

Multipotent Mesenchymal Stem Cells ◽

Deficient Mice ◽

Delay Progression

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Combination of Nonwoven Filters and Mesenchymal Stem Cells Reduced Glomerulosclerotic Lesions in Rat Chronic Kidney Disease Models

International Journal of Clinical Medicine ◽

10.4236/ijcm.2019.103014 ◽

2019 ◽

Vol 10 (03) ◽

pp. 135-149

Author(s):

Hideo Hori ◽

Masanori Shinzato ◽

Yoshiyuki Hiki ◽

Shigeru Nakai ◽

Gen Niimi ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Kidney Disease ◽

Disease Models

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P0026METFORMIIN IMPROVES DYSFUNCTION OF MESENCHYMAL STEM CELLS ASSOCIATED WITH CHRONIC KIDNEY DISEASE VIA SENESCENCE INHIBITION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0026 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Hyunjin Noh ◽

Mi Ra Yu ◽

Kyoungin Choi ◽

Dohui Hwang

Keyword(s):

Chronic Kidney Disease ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Kidney Disease ◽

Cellular Senescence ◽

Critical Factor ◽

Protective Role ◽

Metformin Treatment ◽

Promising Source

Abstract Background and Aims Mesenchymal stem cells (MSC) are promising source of cell-based regenerative therapy; however, adequate cell functionality is a critical factor for the success of autotransplantation. Method We investigated the effects of metformin on chronic kidney disease (CKD)-associated cellular senescence using MSC isolated from sham operated and subtotal nephrectomized mice and further explored the protective role of metformin-treated CKD MSC in renal progression. Results When compared to normal MSC, MSC isolated from CKD mice displayed reduced proliferation and early senescence as determined by enlarged cell morphology, increased oxidative stress, accumulation of DNA damage response marker p53 binding protein 1 (53BP1), phospho p53, p16INK4a, and β-gal expression, and decreased cyclin-dependent kinase 4 (CDK4) and cyclin D. CKD MSC exhibited activation of NFκB resulting in expression of senescence-associated secretory phenotype (SASP) factors compared to normal MSC. All of these changes were significantly prevented by metformin treatment. In vivo, metformin-treated CKD MSC attenuated inflammation and fibrosis in UUO kidney as compared to CKD MSC. Co-culture of LPS or TGF-β1-treated HK2 cells with metformin-treated CKD MSC markedly decreased LPS or TGF-β-induced tubular expression of proinflammatory markers and fibrogenesis when compared to CKD MSC suggesting paracrine action of CKD MSC enhanced by metformin treatment. Conclusion Our data suggest that metformin inhibits cellular senescence of CKD MSC and improves their renoprotective effects.

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Potential and Therapeutic Efficacy of Cell-based Therapy Using Mesenchymal Stem Cells for Acute/chronic Kidney Disease

International Journal of Molecular Sciences ◽

10.3390/ijms20071619 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1619 ◽

Cited By ~ 11

Author(s):

Chul Yun ◽

Sang Lee

Keyword(s):

Chronic Kidney Disease ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Kidney Disease ◽

Therapeutic Efficacy ◽

Inflammatory Responses ◽

Tissue Injury ◽

Kidney Diseases ◽

Diverse Range ◽

Cell Based Therapy

Kidney disease can be either acute kidney injury (AKI) or chronic kidney disease (CKD) and it can lead to the development of functional organ failure. Mesenchymal stem cells (MSCs) are derived from a diverse range of human tissues. They are multipotent and have immunomodulatory effects to assist in the recovery from tissue injury and the inhibition of inflammation. Numerous studies have investigated the feasibility, safety, and efficacy of MSC-based therapies for kidney disease. Although the exact mechanism of MSC-based therapy remains uncertain, their therapeutic value in the treatment of a diverse range of kidney diseases has been studied in clinical trials. The use of MSCs is a promising therapeutic strategy for both acute and chronic kidney disease. The mechanism underlying the effects of MSCs on survival rate after transplantation and functional repair of damaged tissue is still ambiguous. The paracrine effects of MSCs on renal recovery, optimization of the microenvironment for cell survival, and control of inflammatory responses are thought to be related to their interaction with the damaged kidney environment. This review discusses recent experimental and clinical findings related to kidney disease, with a focus on the role of MSCs in kidney disease recovery, differentiation, and microenvironment. The therapeutic efficacy and current applications of MSC-based kidney disease therapies are also discussed.

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