Dual Role of MSC-Derived Exosomes in Tumor Development

Zhao, Rou; Chen, Xinke; Song, Hui; Bie, Qingli; Zhang, Bin

doi:10.1155/2020/8844730

Cited by 40 publications

(34 citation statements)

References 89 publications

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“…Exosomes exceed MSCs in sustainability and scalability as they are more stable than MSCs [ 25 , 78 ]. However, their tumorigenic potential is debatable, as some studies support their tumor promotion potential, whereas others support their tumor inhibitory potential [ 79 ]. Preclinical and clinical studies have demonstrated the effects of exosomes in reducing cytokine storm complications, such as alveolar inflammation, edema, and epithelial tissue regeneration in inflammatory diseases, such as ARDS, asthma, COPD, and acute lung injury (ALI) [ 25 , 80 – 86 ].…”

Section: Msc-derived Exosomes and Covid-19mentioning

confidence: 99%

Mesenchymal stem cell-based therapy and exosomes in COVID-19: current trends and prospects

et al. 2021

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Novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2. The virus causes an exaggerated immune response, resulting in a cytokine storm and acute respiratory distress syndrome, the leading cause of COVID-19-related mortality and morbidity. So far, no therapies have succeeded in circumventing the exacerbated immune response or cytokine storm associated with COVID-19. Mesenchymal stem cells (MSCs), through their immunomodulatory and regenerative activities, mostly mediated by their paracrine effect and extracellular vesicle production, have therapeutic potential in many autoimmune, inflammatory, and degenerative diseases. In this paper, we review clinical studies on the use of MSCs for COVID-19 treatment, including the salutary effects of MSCs on the pathophysiology of COVID-19 and the immunomodulation of the cytokine storm. Ongoing clinical trial designs, cell sources, dose and administration, and populations are summarized, and the paracrine mode of benefit is discussed. We also offer suggestions for optimizing MSC-based therapies, including genetic engineering, strategies for cell surface modification, nanotechnology applications, and combination therapies.

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Section: Msc-derived Exosomes and Covid-19mentioning

confidence: 99%

Mesenchymal stem cell-based therapy and exosomes in COVID-19: current trends and prospects

et al. 2021

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“…Although MSCs are expected to be developed as drug delivery vehicles, several studies have reported that MSCs support the construction of the tumor microenvironment by differentiation into cancer (carcinoma-, tumor-)-associated fibroblasts (CAFs) [23,68], as well as accelerate tumor growth and metastasis by stimulating tumor cells via direct cell-cell interactions and tumor cell-derived extracellular vesicles (EVs) [68][69][70][71]. CAFs closely resemble myofibroblasts and express α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP) [72].…”

Section: Differentiation Capacity Of Mscs To Cancer-associated Fibroblastsmentioning

confidence: 99%

“…Several studies have suggested that EVs secreted from MSCs in tumor tissues promote tumor growth and metastasis. It has been reported that microRNA-15a, 21, 34a, 191, 125a, 140, and 222/223 in MSC-derived EVs improved the resistance to anti-cancer drugs, proliferation, migration of cancer cells, and angiogenesis by tumor stromal cells [69]. However, studies have also reported that MSCderived EVs possess anti-tumor effects [69].…”

Section: Influence Of Msc-derived Evs On Tumor Progressionmentioning

confidence: 99%

“…It has been reported that microRNA-15a, 21, 34a, 191, 125a, 140, and 222/223 in MSC-derived EVs improved the resistance to anti-cancer drugs, proliferation, migration of cancer cells, and angiogenesis by tumor stromal cells [69]. However, studies have also reported that MSCderived EVs possess anti-tumor effects [69]. Therefore, it remains unclear whether MSC-derived EVs exhibit pro-or antitumorigenic effects.…”

Section: Influence Of Msc-derived Evs On Tumor Progressionmentioning

confidence: 99%

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Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics

Takayama

Kusamori

Nishikawa

2021

Expert Opinion on Drug Delivery

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Introduction: Drug delivery to solid tumors remains a significant therapeutic challenge. Mesenchymal stem/stromal cells (MSCs) home to tumor tissues and can be employed as tumor targeted drug/gene delivery vehicles. Reportedly, therapeutic gene-or anti-cancer drug-loaded MSCs have shown remarkable anti-tumor effects in preclinical studies, and some clinical trials for assessing therapeutic MSCs in patients with cancer have been registered. Areas covered: In the present review, we first discuss the source and interdonor heterogeneity of MSCs, their tumor-homing mechanism, and the route of MSC administration in MSC-based cancer therapy. We then summarize the therapeutic applications of MSCs as a drug delivery vehicle for therapeutic genes or anti-cancer drugs and the drug delivery mechanism from drug-loaded MSCs to cancer cells. Expert opinion: Although numerous preclinical studies have revealed significant anti-tumor effects, several clinical trials assessing MSC-based cancer gene therapy have failed to demonstrate corroborative results, documenting limited therapeutic effects. Notably, a successful clinical outcome with MSC-based cancer therapy would require the interdonor heterogeneity of administered MSCs to be resolved, along with improved tumor-homing efficiency and optimized drug delivery efficiency from MSCs to cancer cells.

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“…MSC can upregulate tumour PD-L1 [ 151 ] and are important tumour microenvironment regulators [ 152 ]. MSC can self-renew, have a multidirectional differentiation potential, and efflux large quantities of exosomes, thereby potentially acting as a hub to integrate and influence signals across the tumour microenvironment [ 153 ]. MSC can release mitochondria, both directly and within extracellular vesicles, which can be taken up by other cells, which may be a treatment target [ 154 ].…”

Section: Wider Regulators Of the Tumour Microenvironment And Immunmentioning

confidence: 99%

Tumour Microenvironment: Roles of the Aryl Hydrocarbon Receptor, O-GlcNAcylation, Acetyl-CoA and Melatonergic Pathway in Regulating Dynamic Metabolic Interactions across Cell Types—Tumour Microenvironment and Metabolism

Anderson¹

2020

IJMS

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This article reviews the dynamic interactions of the tumour microenvironment, highlighting the roles of acetyl-CoA and melatonergic pathway regulation in determining the interactions between oxidative phosphorylation (OXPHOS) and glycolysis across the array of cells forming the tumour microenvironment. Many of the factors associated with tumour progression and immune resistance, such as yin yang (YY)1 and glycogen synthase kinase (GSK)3β, regulate acetyl-CoA and the melatonergic pathway, thereby having significant impacts on the dynamic interactions of the different types of cells present in the tumour microenvironment. The association of the aryl hydrocarbon receptor (AhR) with immune suppression in the tumour microenvironment may be mediated by the AhR-induced cytochrome P450 (CYP)1b1-driven ‘backward’ conversion of melatonin to its immediate precursor N-acetylserotonin (NAS). NAS within tumours and released from tumour microenvironment cells activates the brain-derived neurotrophic factor (BDNF) receptor, TrkB, thereby increasing the survival and proliferation of cancer stem-like cells. Acetyl-CoA is a crucial co-substrate for initiation of the melatonergic pathway, as well as co-ordinating the interactions of OXPHOS and glycolysis in all cells of the tumour microenvironment. This provides a model of the tumour microenvironment that emphasises the roles of acetyl-CoA and the melatonergic pathway in shaping the dynamic intercellular metabolic interactions of the various cells within the tumour microenvironment. The potentiation of YY1 and GSK3β by O-GlcNAcylation will drive changes in metabolism in tumours and tumour microenvironment cells in association with their regulation of the melatonergic pathway. The emphasis on metabolic interactions across cell types in the tumour microenvironment provides novel future research and treatment directions.

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Dual Role of MSC-Derived Exosomes in Tumor Development

Cited by 40 publications

References 89 publications

Mesenchymal stem cell-based therapy and exosomes in COVID-19: current trends and prospects

Mesenchymal stem cell-based therapy and exosomes in COVID-19: current trends and prospects

Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics

Tumour Microenvironment: Roles of the Aryl Hydrocarbon Receptor, O-GlcNAcylation, Acetyl-CoA and Melatonergic Pathway in Regulating Dynamic Metabolic Interactions across Cell Types—Tumour Microenvironment and Metabolism

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