Effects of Human Umbilical Cord Mesenchymal Stem Cells on Renal Ischaemia-reperfusion Injury in Rats

Qiu, Zhenyu; Dun, Zhou; Sun, Dingyong

doi:10.1590/s1677-5538.ibju.2014.04.16

Cited by 8 publications

(3 citation statements)

References 25 publications

(24 reference statements)

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“…However, there are numerous studies indicating the benefits of therapy with mesenchymal stem cells in the recovery process of AKI through various mechanisms, including anti-inflammation, anti-apoptosis, antifibrosis, immunomodulation, and proangiogenesis [ 31 ]. These mesenchymal stem cells are derived from many different tissues and organs, such as dental pulp [ 32 ], amniotic fluid [ 33 ], umbilical cord [ 34 ], and bone marrow [ 35 , 36 ]. Our studies on uterine stem cells are further supported by a recent study showing that uterine-derived feline mesenchymal stem cells (UMSCs) have a therapeutic effect on chronic kidney disease (CKD) in cats [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic role of uterine-derived stem cells in acute kidney injury

et al. 2022

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Background Acute kidney injury (AKI) causes abrupt deterioration in kidney function that disrupts metabolic, electrolyte and fluid homeostasis. Although the prevalence of AKI is steadily increasing, no definitive treatment options are available, leading to severe morbidity and mortality. We evaluated the role of uterine-derived multipotent stem cells in kidney regeneration after ischemic AKI. Methods Female C57BL/6J mice were hysterectomized and subsequently subject to AKI by either unilateral or bilateral renal ischemia–reperfusion injury. Uterine-derived cells (UDCs), containing a population of uterine stem cells, were isolated from the uteri of female transgenic DsRed mice and injected intravenously to AKI mice. Engraftment of DsRed cells was analyzed by flow cytometry while serum creatinine levels were determined colorimetrically. Expression of UDC markers and cytokine markers were analyzed by immunohistochemical and qRT-PCR methods, respectively. The Kaplan–Meier method was used to analyze survival time while unpaired t test with Welch’s correction used for data analysis between two groups. Results Mice with an intact uterus, and hence an endogenous source of UDCs, had a higher survival rate after bilateral ischemic AKI compared to hysterectomized mice. Mice treated with infusion of exogenous UDCs after hysterectomy/AKI had lower serum creatinine levels and higher survival rates compared to controls that did not receive UDCs. Engraftment of labeled UDCs was significantly higher in kidneys of bilateral ischemic AKI mice compared to those that underwent a sham surgery. When unilateral ischemic AKI was induced, higher numbers of UDCs were found in the injured than non-injured kidney. Immunofluorescence staining demonstrated double-positive DsRed/Lotus tetragonolobus agglutinin (LTA) positive cells and DsRed/CD31 positive cells indicating contribution of UDCs in renal tubular and vascular regeneration. Expression of Cxcl12, Bmp2, Bmp4, and Ctnf in renal tissue was significantly higher in the UDCs injection group than the control group. Conclusions UDCs engrafted injured kidneys, contributed to proximal tubule and vascular regeneration, improved kidney function and increased survival in AKI mice. UDC administration is a promising new therapy for AKI. Endogenous uterine stem cells likely also preserve kidney function, suggesting a novel interaction between the uterus and kidney. We suggest that hysterectomy may have a detrimental effect on response to renal injury.

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Section: Discussionmentioning

confidence: 99%

Therapeutic role of uterine-derived stem cells in acute kidney injury

et al. 2022

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“…Currently, the majority of studies have suggested that IRI is associated with the excessive production of oxygen free radicals, calcium overload, inflammatory response, energy metabolism disorders and apoptosis (17–19). Apoptosis is an important cause of severe liver damage and organ dysfunction during ischemia-reperfusion (20,21).…”

Section: Discussionmentioning

confidence: 99%

Expression of tubulin folding cofactor B in mouse hepatic ischemia-reperfusion injury

et al. 2017

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Abstract. The aim of the present study was to investigate the association between tubulin folding cofactor B (TBCB) expression and ischemia-reperfusion injury (IRI) in mice. A total of 48 C57BL/6 mice were randomly divided into a control group (Sham, n=6) and an ischemia-reperfusion group (n=42). The ischemia-reperfusion group was further divided into 6 subgroups as per different times after reperfusion (2,4,6,8,12 and 24 h), with 7 mice per subgroup. A hepatic IRI model was established in mice by clamping the hepatic hilum. Morphology, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), and the expression level of TBCB were detected. Compared with the control group, the livers from the ischemia-reperfusion group were significantly changed, particularly at 12 h following ischemia-reperfusion, with obvious hepatic cell degeneration and necrosis. The ALT, AST, IL-6 and TNF-α levels in the sera of the mice in the hepatic ischemia-reperfusion group were increased at all time points following ischemia-reperfusion, and were the highest at 12 h, demonstrating statistically significant differences when compared with the control group (P<0.05). Furthermore, the expression levels of TBCB, TNF-α and IL-6 were significantly increased at all time-points following ischemia-reperfusion, and were the most significant at 12 h. At 24 h following ischemia-reperfusion, the expression levels had decreased. The present study indicated that TBCB expression is associated with TNF-α and IL-6 expression levels in mice with hepatic ischemia-reperfusion, and may be key in the development of liver injury during ischemia-reperfusion in mice.

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“…In a renal allograft transplantation model in rat, intra-arterial MSC injection resulted in improved early kidney function, reduction of lymphocyte infiltration, and decreased inflammation-related gene expression [91]. MSC have been shown to reduce infiltration of immune cells in the kidney after MSC infusion in rats [92,93], and they were also able to prevent renal fibrosis interacting with the renin-angiotensin system [94].…”

Section: Msc In Kidney Injury Animal Modelsmentioning

confidence: 99%

Mesenchymal Stromal Cells as Anti-Inflammatory and Regenerative Mediators for Donor Kidneys During Normothermic Machine Perfusion

Sierra-Parraga

Eijken

Hunter

et al. 2017

Stem Cells and Development

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There is great demand for transplant kidneys for the treatment of end-stage kidney disease patients. To expand the donor pool, organs from older and comorbid brain death donors, so-called expanded criteria donors (ECD), as well as donation after circulatory death donors, are considered for transplantation. However, the quality of these organs may be inferior to standard donor organs. A major issue affecting graft function and survival is ischemia/reperfusion injury, which particularly affects kidneys from deceased donors. The development of hypothermic machine perfusion has been introduced in kidney transplantation as a preservation technique and has improved outcomes in ECD and marginal organs compared to static cold storage. Normothermic machine perfusion (NMP) is the most recent evolution of perfusion technology and allows assessment of the donor organ before transplantation. The possibility to control the content of the perfusion fluid offers opportunities for damage control and reparative therapies during machine perfusion. Mesenchymal stromal cells (MSC) have been demonstrated to possess potent regenerative properties via the release of paracrine effectors. The combination of NMP and MSC administration at the same time is a promising procedure in the field of transplantation. Therefore, the MePEP consortium has been created to study this novel modality of treatment in preparation for human trials. MePEP aims to assess the therapeutic effects of MSC administered ex vivo by NMP in the mechanisms of injury and repair in a porcine kidney autotransplantation model.

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Effects of Human Umbilical Cord Mesenchymal Stem Cells on Renal Ischaemia-reperfusion Injury in Rats

Cited by 8 publications

References 25 publications

Therapeutic role of uterine-derived stem cells in acute kidney injury

Therapeutic role of uterine-derived stem cells in acute kidney injury

Expression of tubulin folding cofactor B in mouse hepatic ischemia-reperfusion injury

Mesenchymal Stromal Cells as Anti-Inflammatory and Regenerative Mediators for Donor Kidneys During Normothermic Machine Perfusion

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