Mesenchymal Stromal Cell Uses for Acute Kidney Injury—Current Available Data and Future Perspectives: A Mini-Review

Zilberman-Itskovich, Shani; Efrati, Shai

doi:10.3389/fimmu.2020.01369

Cited by 14 publications

(10 citation statements)

References 66 publications

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“…As noted above, AKI is usually associated with disorders and abnormal activation of the immune system, which can in turn be affected by treatment with MSCs and their EVs, suggesting that utilizing and modifying EVs to regulate the immunomicroenvironment might be an efficient and effective therapeutic approach for AKI (100)(101)(102)(103)(104)(105)(106). Although some researchers have reported that MSCs and MSC-EVs can affect the immune function and immune microenvironment in AKI both in vitro and in vivo, the findings have been inconsistent (107).…”

Section: Evs Participate In the Immune Regulation Of Mscs In Akimentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapeutic Strategy for Acute Kidney Injury

Yang

et al. 2021

Front. Immunol.

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Acute kidney injury (AKI) is a common and potential life-threatening disease in patients admitted to hospital, affecting 10%–15% of all hospitalizations and around 50% of patients in the intensive care unit. Severe, recurrent, and uncontrolled AKI may progress to chronic kidney disease or end-stage renal disease. AKI thus requires more efficient, specific therapies, rather than just supportive therapy. Mesenchymal stem cells (MSCs) are considered to be promising cells for cellular therapy because of their ease of harvesting, low immunogenicity, and ability to expand in vitro. Recent research indicated that the main therapeutic effects of MSCs were mediated by MSC-derived extracellular vesicles (MSC-EVs). Furthermore, compared with MSCs, MSC-EVs have lower immunogenicity, easier storage, no tumorigenesis, and the potential to be artificially modified. We reviewed the therapeutic mechanism of MSCs and MSC-EVs in AKI, and considered recent research on how to improve the efficacy of MSC-EVs in AKI. We also summarized and analyzed the potential and limitations of EVs for the treatment of AKI to provide ideas for future clinical trials and the clinical application of MSC-EVs in AKI.

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Section: Evs Participate In the Immune Regulation Of Mscs In Akimentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapeutic Strategy for Acute Kidney Injury

Yang

et al. 2021

Front. Immunol.

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“…Clinical trials with MSC administration in patients with AKI or sepsis-associated AKI, chronic kidney disease or diabetic nephropathy has been limited to a small number of early phase clinical trials. Overall, MSC demonstrated good safety and tolerability, however only modest alterations in plasma cytokine profiles were observed, without a clear signal of improved outcome for MSC-treated patients [ [156] , [157] , [158] ].…”

Section: Mscs-based Therapies For Multiple Organs Affected By Covid-1mentioning

confidence: 99%

Therapeutic potential of mesenchymal stem cells in multiple organs affected by COVID-19

et al. 2021

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Currently, the world has been devastated by an unprecedented pandemic in this century. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the agent of coronavirus disease 2019 (COVID-19), has been causing disorders, dysfunction and morphophysiological alterations in multiple organs as the disease evolves. There is a great scientific community effort to obtain a therapy capable of reaching the multiple affected organs in order to contribute for tissue repair and regeneration. In this regard, mesenchymal stem cells (MSCs) have emerged as potential candidates concerning the promotion of beneficial actions at different stages of COVID-19. MSCs are promising due to the observed therapeutic effects in respiratory preclinical models, as well as in cardiac, vascular, renal and nervous system models. Their immunomodulatory properties and secretion of paracrine mediators, such as cytokines, chemokines, growth factors and extracellular vesicles allow for long range tissue modulation and, particularly, blood-brain barrier crossing. This review focuses on SARS-CoV-2 impact to lungs, kidneys, heart, vasculature and central nervous system while discussing promising MSC's therapeutic mechanisms in each tissue. In addition, MSC's therapeutic effects in high-risk groups for COVID-19, such as obese, diabetic and hypertensive patients are also explored.

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“…Renal tubular epithelial cell (RTEC) injury due to ischemia-reperfusion injury (IRI), nephrotoxicity and other causes lead to a rapid decline in renal function and over-activated inflammatory immune response. If the inflammatory damage to RTEC was not controlled timely, a continuous renal injury would result in renal fibrosis and failure (1)(2)(3). Unfortunately, current pharmacological interventions have failed to prevent intrarenal inflammatory cascade.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell Protects Injured Renal Tubular Epithelial Cells by Regulating mTOR-Mediated Th17/Treg Axis

Luo

Guo

Zhang³

et al. 2021

Front. Immunol.

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The increase in T helper 17 cell (Th17)-mediated pro-inflammatory response and decrease in regulatory T cell (Treg)-mediated anti-inflammatory effect aggravate renal tubular epithelial cell (RTEC) injury. However, increasing evidence indicated that mesenchymal stem cell (MSC) possessed the ability to control the imbalance between Th17 and Treg. Given that Th17 and Treg are derived from a common CD4+ T cell precursor, we summarize the current knowledge of MSC-mediated inhibition of the mammalian target of rapamycin (mTOR), which is a master regulator of CD4+ T cell polarization. During CD4+ T cell differentiation, mTOR signaling mediates Th17 and Treg differentiation via hypoxia-inducible factor-1α (HIF-1α)-dependent metabolic regulation and signaling pathway, as well as mTOR-mediated phosphorylation of signal transducer and activator of transcription (STAT) 3 and 5. Through interfering with mTOR signaling, MSC restrains CD4+ T cell differentiation into Th17, but in turn promotes Treg generation. Thus, this review indicates that MSC-mediated Th17-to-Treg polarization is expected to act as new immunotherapy for kidney injury.

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Mesenchymal Stromal Cell Uses for Acute Kidney Injury—Current Available Data and Future Perspectives: A Mini-Review

Cited by 14 publications

References 66 publications

Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapeutic Strategy for Acute Kidney Injury

Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapeutic Strategy for Acute Kidney Injury

Therapeutic potential of mesenchymal stem cells in multiple organs affected by COVID-19

Mesenchymal Stem Cell Protects Injured Renal Tubular Epithelial Cells by Regulating mTOR-Mediated Th17/Treg Axis

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