In a Phase 1a escalating clinical trial, autologous mesenchymal stem cell infusion for renovascular disease increases blood flow and the glomerular filtration rate while reducing inflammatory biomarkers and blood pressure

Abumoawad, Abdelrhman; Saad, Ahmed; Ferguson, Christopher M.; Eirin, Alfonso; Herrmann, Sandra M.; Hickson, La Tonya J.; Goksu, Busra B.; Bendel, Emily C.; Misra, Sanjay; Glockner, James F.; Dietz, Allan B.; Lerman, Lilach O.; Textor, Stephen C.

doi:10.1016/j.kint.2019.11.022

Cited by 53 publications

(42 citation statements)

References 45 publications

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“…MSC treatment was not effective in reducing BP and expression of inflammatory cytokines in the STK except for IL‐6, possibly because of the severity of the insult, single treatment, and short‐term observation. Amelioration of RVH in mice may require repeated MSC delivery (Oliveira‐Sales et al, 2013), and in humans appear to be dose‐dependent (Abumoawad et al, 2020). However, we have previously shown that single delivery of MSCs is effective in improving kidney function and decreasing injury in the swine STK (Eirin et al, 2014), and the dose we used evidently sufficed to normalize renal function.…”

Section: Discussionmentioning

confidence: 99%

“…MSC treatment was not effective in reducing BP and expression of inflammatory cytokines in the STK except for IL-6, possibly because of the severity of the insult, single treatment, and short-term observation. Amelioration of RVH in mice may require repeated MSC delivery (Oliveira-Sales et al, 2013), and in humans appear to be dose-dependent (Abumoawad et al, 2020).…”

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confidence: 99%

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Increased cellular senescence in the murine and human stenotic kidney: Effect of mesenchymal stem cells

Kim

Zou

Tang

et al. 2020

Journal Cellular Physiology

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Cell stress may give rise to insuperable growth arrest, which is defined as cellular senescence. Stenotic kidney (STK) ischemia and injury induced by renal artery stenosis (RAS) may be associated with cellular senescence. Mesenchymal stem cells (MSCs) decrease some forms of STK injury, but their ability to reverse senescence in RAS remains unknown. We hypothesized that RAS evokes STK senescence, which would be ameliorated by MSCs. Mice were studied after 4 weeks of RAS, RAS treated with adipose tissue-derived MSCs 2 weeks earlier, or sham. STK senescenceassociated β-galactosidase (SA-β-Gal) activity was measured. Protein and gene expression was used to assess senescence and the senescence-associated secretory phenotype (SASP), and staining for renal fibrosis, inflammation, and capillary density. In addition, senescence was assessed as p16+ and p21+ urinary exosomes in patients with renovascular hypertension (RVH) without or 3 months after autologous adipose tissue-derived MSC delivery, and in healthy volunteers (HV). In RAS mice, STK SA-β-Gal activity increased, and senescence and SASP marker expression was markedly elevated. MSCs improved renal function, fibrosis, inflammation, and capillary density, and attenuated SA-β-Gal activity, but most senescence and SASP levels remained unchanged. Congruently, in human RVH, p21+ urinary exosomes were elevated compared to HV, and only slightly improved by MSC, whereas p16+ exosomes remained unchanged. Therefore, RAS triggers renal senescence in both mice and human subjects. MSCs decrease renal injury, but only partly mitigate renal senescence. These observations support exploration of targeted senolytic therapy in RAS.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Increased cellular senescence in the murine and human stenotic kidney: Effect of mesenchymal stem cells

Kim

Zou

Tang

et al. 2020

Journal Cellular Physiology

Self Cite

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“…Animal experiments have confirmed that the combination of MSCs with ARVD to treat atherosclerotic renal artery stenosis helps to restore functions of the kidney [90]. Thereafter, several clinical trials have evinced the safety of infusing autologous ADMSCs in the treatment of ARVD [91][92][93]. Following this, ADMSC-EVs have also become the focus of recent research.…”

Section: Msc-evs and Atherosclerotic Renovascular Diseasesmentioning

confidence: 97%

Mesenchymal stem cells and extracellular vesicles in therapy against kidney diseases

Huang

Yang

2021

Stem Cell Res Ther

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Kidney diseases pose a threat to human health due to their rising incidence and fatality rate. In preclinical and clinical studies, it has been acknowledged that mesenchymal stem cells (MSCs) are effective and safe when used to treat kidney diseases. MSCs play their role mainly by secreting trophic factors and delivering extracellular vesicles (EVs). The genetic materials and proteins contained in the MSC-derived EVs (MSC-EVs), as an important means of cellular communication, have become a research focus for targeted therapy of kidney diseases. At present, MSC-EVs have shown evident therapeutic effects on acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy (DN), and atherosclerotic renovascular disease (ARVD); however, their roles in the transplanted kidney remain controversial. This review summarises the mechanisms by which MSC-EVs treat these diseases in animal models and proposes certain problems, expecting to facilitate corresponding future clinical practice.

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“…Blood flow, renal parameters, blood pressure and inflammatory markers were examined prior to infusion and 3‐months post‐infusion. Administration of autologous adipose‐derived mesenchymal stem cells increased blood flow and glomerular filtration rate while it decreased blood pressure and inflammation 111 . Although a precise role for KLF5 in generation of adipose‐derived mesenchymal stem cells is unknown, KLF5 has been identified as an important regulator of adipocyte differentiation 52,112 …”

Section: The Current and Possible Functions Regulatory Mechanisms Ofmentioning

confidence: 99%

Roles of Krüppel‐like factor 5 in kidney disease

Liu

Zhou

et al. 2021

J Cellular Molecular Medi

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Transcription factor Krüppel‐like factor 5 (KLF5) is a member of the Krüppel‐like factors’ (KLFs) family. KLF5 regulates a number of cellular functions, such as apoptosis, proliferation and differentiation. Therefore, KLF5 can play a role in many diseases, including, cancer, cardiovascular disease and gastrointestinal disorders. An important role for KLF5 in the kidney was recently reported, such that KLF5 regulated podocyte apoptosis, renal cell proliferation, tubulointerstitial inflammation and renal fibrosis. In this review, we have summarized the available information in the literature with a brief description on how transcriptional, post‐transcriptional and post‐translational modifications of KLF5 modulate its function in a variety of organs including the kidney with a focus of its importance on the pathogenesis of various kidney diseases. Furthermore, we also have outlined the current and possible mechanisms of KLF5 activation in kidney diseases. These studies suggest a need for more systemic investigations, particularly for generation of animal models with renal cell‐specific deletion or overexpression of KLF5 gene to examine direct contributions of KLF5 to various kidney diseases. This will promote further experimentation in the development of therapies to prevent or treat various kidney diseases.

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In a Phase 1a escalating clinical trial, autologous mesenchymal stem cell infusion for renovascular disease increases blood flow and the glomerular filtration rate while reducing inflammatory biomarkers and blood pressure

Cited by 53 publications

References 45 publications

Increased cellular senescence in the murine and human stenotic kidney: Effect of mesenchymal stem cells

Increased cellular senescence in the murine and human stenotic kidney: Effect of mesenchymal stem cells

Mesenchymal stem cells and extracellular vesicles in therapy against kidney diseases

Roles of Krüppel‐like factor 5 in kidney disease

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