Human Mesenchymal Stem Cell Secretome from Bone Marrow or Adipose-Derived Tissue Sources for Treatment of Hypoxia-Induced Pulmonary Epithelial Injury

Shologu, Nala; Scully, Michael; Laffey, John G.; O’Toole, Daniel

doi:10.3390/ijms19102996

Cited by 41 publications

(36 citation statements)

References 74 publications

(81 reference statements)

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“…MSCs expedite and promote recovery in animal models of ALI which include Escherichia coli endotoxin-induced, hypoxia-induced, LPS-induced and ventilator induced lung injury [134][135][136][137][138]. In a systematic review of 17 published preclinical animal model studies that reported on mortality, McIntyre et al were able to show that treatment with MSCs, as compared to controls, significantly decreased the overall odds of death in animals with acute lung injury [139].…”

Section: Preclinical Studies Of Msc Therapy In Acute Lung Injury (Ali)mentioning

confidence: 99%

“…In a systematic review of 17 published preclinical animal model studies that reported on mortality, McIntyre et al were able to show that treatment with MSCs, as compared to controls, significantly decreased the overall odds of death in animals with acute lung injury [139]. In these models, the mechanism of the repair process is attributed to inhibiting TNF-α release, enhancing IL-10 secretion, decreasing IL-6 levels, increasing KGF, overexpression of angiopoietin-1, reprogramming of macrophage function and secretion of antimicrobial peptides [137,138].…”

Section: Preclinical Studies Of Msc Therapy In Acute Lung Injury (Ali)mentioning

confidence: 99%

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Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients

et al. 2020

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In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan, capital city of Hubei province in China. Cases of SARS-CoV-2 infection quickly grew by several thousand per day. Less than 100 days later, the World Health Organization declared that the rapidly spreading viral outbreak had become a global pandemic. Coronavirus disease 2019 (COVID-19) is typically associated with fever and respiratory symptoms. It often progresses to severe respiratory distress and multi-organ failure which carry a high mortality rate. Older patients or those with medical comorbidities are at greater risk for severe disease. Inflammation, pulmonary edema and an over-reactive immune response can lead to hypoxia, respiratory distress and lung damage. Mesenchymal stromal/stem cells (MSCs) possess potent and broad-ranging immunomodulatory activities. Multiple in vivo studies in animal models and ex vivo human lung models have demonstrated the MSC's impressive capacity to inhibit lung damage, reduce inflammation, dampen immune responses and aid with alveolar fluid clearance. Additionally, MSCs produce molecules that are antimicrobial and reduce pain. Upon administration by the intravenous route, the cells travel directly to the lungs where the majority are sequestered, a great benefit for the treatment of pulmonary disease. The in vivo safety of local and intravenous administration of MSCs has been demonstrated in multiple human clinical trials, including studies of acute respiratory distress syndrome (ARDS). Recently, the application of MSCs in the context of ongoing COVID-19 disease and other viral respiratory illnesses has demonstrated reduced patient mortality and, in some cases, improved long-term pulmonary function. Adipose-derived stem cells (ASC), an abundant type of MSC, are proposed as a therapeutic option for the treatment of COVID-19 in order to reduce morbidity and mortality. Additionally, when proven to be safe and effective, ASC treatments may reduce the demand on critical hospital resources. The ongoing COVID-19 outbreak has resulted in significant healthcare and socioeconomic burdens across the globe. There is a desperate need for safe and effective treatments. Cellular based therapies hold great promise for the treatment of COVID-19. This literature summary reviews the scientific rationale and need for clinical studies of adipose-derived stem cells and other types of mesenchymal stem cells in the treatment of patients who suffer with COVID-19.

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Section: Preclinical Studies Of Msc Therapy In Acute Lung Injury (Ali)mentioning

confidence: 99%

Section: Preclinical Studies Of Msc Therapy In Acute Lung Injury (Ali)mentioning

confidence: 99%

Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients

et al. 2020

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“…However, data correlated to the molecular and cellular mechanisms underlying hypoxic and reperfusion lung damage are limited. Moreover, the majority of the studies are focused on endothelial and epithelial cells rather than alveolar macrophages that have critical immunological functions in acute lung injuries including ischemia reperfusion lung injury [10,17,19,20].…”

Section: Discussionmentioning

confidence: 99%

Interferon regulatory factor 8 induces alveolar macrophage hypoxia/reoxygenation injury via the PINK1/Parkin mitophagy pathway

Zhang¹,

Hu²,

He³

et al. 2020

Preprint

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Background: Lung ischemia-reperfusion injury (LIRI) is a complex process and macrophages play a central role in it. Interferon regulatory factor 8 (IRF8) is a transcription factor in the innate immune system, which, together with autophagy, are important components of the mechanisms of LIRI. We aimed to explore the regulatory role of IRF8 in hypoxia/reoxygenation (HR) injury and PINK1-mediated mitophagy.Methods: Cultured NR8383 macrophages were subjected to HR as an in vitro model of LIRI. Cell viability, cell damage and inflammation during HR were evaluated by Cell Counting Kit-8 assay, lactate dehydrogenase assessment and enzyme linked immunosorbent assay, respectively. Meanwhile, PINK1/Parkin-mediated mitochondrial autophagy was detected by quantitative real-time PCR, western blot, transmission electron microscopy and double immunofluorescence labeling method. The effects of IRF8 and PINK1 on cell injury, inflammatory response and autophagy during HR were assessed using IRF8 short-hairpin RNA plasmids and PINK1 overexpression plasmids , respectively. Results: IRF8 inhibition was able to alleviate cell injury, inflammatory response and autophagy while PINK1 overexpression could exacerbate them. Moreover, IRF8 downregulation could reduce the expression of PINK1 in HR injury and attenuate the effects of it. Conclusion: IRF8 was able to induce HR injury via the PINK1/Parkin mitophagy pathway. Inhibition of IRF8 and PINK1/Parkin-mediated mitophagy might be a potential target for the treatment of LIRI.

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“…Mesenchymal stem cells (MSCs) are the most widely used cell type for cell transplantation‐based treatments, because of their ability to differentiate into multiple lineages, as well as the ease in which they can be isolated from different tissue sources and propagated . MSCs derived from bone marrow, adipose tissue, muscles, and ESCs are currently being used to treat various diseases and conditions, such as myocardial ischemia, stroke, and musculoskeletal disease, with the idea being that the transplantation of MSCs near the sites of damaged tissue results in their differentiation and reconstitution of the tissue, such that it regains functionality. For example, percutaneous injection of bone marrow‐derived MSCs into the damaged myocardium in a pig model of myocardial ischemia reduced the extent of necrosis, promoted the regeneration of contractile myocardium, and improved overall cardiac function …”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles and their roles in stem cell biology

2020

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Stem cells use a variety of mechanisms to help maintain their pluripotency and promote self‐renewal, as well as, at the appropriate time, to differentiate into specialized cells. One such mechanism that is attracting significant attention from the stem cell, development, and regenerative medicine research communities involves a form of intercellular communication, specifically, the ability of cells to form and release nontraditional membrane‐enclosed structures, referred to as extracellular vesicles (EVs). There are two major classes of EVs, microvesicles (MVs), which are generated through the outward budding and fission of the plasma membrane, and exosomes, which are formed as multivesicular bodies (MVBs) in the endo‐lysosomal pathway that fuse with the cell surface to release their contents. Although they differ in how they are formed, both MVs and exosomes have been shown to contain a diverse array of bioactive cargo, such as proteins, RNA transcripts, microRNAs, and even DNA, which can be transferred to other cells and promote phenotypic changes. Here, we will describe what is currently known regarding EVs and the roles they play in stem cell biology and different aspects of early development. We will also highlight how the EVs produced by stem cells are being aggressively pursued for clinical applications, including their potential use as therapeutic delivery systems and for their regenerative capabilities.

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Human Mesenchymal Stem Cell Secretome from Bone Marrow or Adipose-Derived Tissue Sources for Treatment of Hypoxia-Induced Pulmonary Epithelial Injury

Cited by 41 publications

References 74 publications

Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients

Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients

Interferon regulatory factor 8 induces alveolar macrophage hypoxia/reoxygenation injury via the PINK1/Parkin mitophagy pathway

Extracellular vesicles and their roles in stem cell biology

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