Biology and therapeutic potential of mesenchymal stem cell‐derived exosomes

Xunian, Zhou; Kalluri, Raghu

doi:10.1111/cas.14563

Cited by 170 publications

(130 citation statements)

References 121 publications

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“…Although the mechanisms of MSC exosome endocytosis have not yet been fully elucidated, several cellular processes including vesicle-cell fusion, phagocytosis, micropinocytosis, and/or receptor-mediated endocytosis are assumed to be involved in internalization [ 29 ]. However, some researchers have claimed that internalization of MSC exosome into target cells is not necessary for them to exert a therapeutic effect [ 30 , 31 ].…”

Section: Therapeutic Properties Of Msc Exosomesmentioning

confidence: 99%

Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

Lee

Kang

2021

JCM

115

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Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.

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Section: Therapeutic Properties Of Msc Exosomesmentioning

confidence: 99%

Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

Lee

Kang

2021

JCM

115

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“…Exosomes are now being implicated in adaptive and immune response regulation. Though we did not observe control exosomes (deprived of STINGa cargo) eliciting measurable immune responses at the dosage reported here, it is possible that added benefit could be realized with iExo STINGa generated from a cell source with potential for T-cell activation ( 37 , 38 ). In this study, the robust antitumor response using iExo STINGa as a single agent with systemic effect on secondary tumors supports the potential of iExo STINGa in clinical use via an established GMP-exosomes production platform ( 26 ).…”

Section: Discussionmentioning

confidence: 56%

Effective delivery of STING agonist using exosomes suppresses tumor growth and enhances antitumor immunity

McAndrews¹,

P.Y.²,

LeBleu³

et al. 2021

Journal of Biological Chemistry

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The Stimulator of Interferon Genes (STING) pathway is implicated in the innate immune response and is important in both oncogenesis and cancer treatment. Specifically, activation of the cytosolic DNA sensor STING in antigen-presenting cells (APCs) induces a type I interferon response and cytokine production that facilitates antitumor immune therapy. However, use of STING agonists (STINGa) as a cancer therapeutic has been limited by unfavorable pharmacological properties and targeting inefficiency due to rapid clearance and limited uptake into the cytosol. Exosomes, a class of extracellular vesicles shed by all cells are under consideration for their use as effective carriers of drugs owing to their innate ability to be taken up by cells and their biocompatibility for optimal drug biodistribution. Therefore, we engineered exosomes to deliver the STING agonist cyclic GMP-AMP (iExo STINGa ), to exploit their favorable pharmacokinetics and pharmacodynamics. Selective targeting of the STING pathway in APCs with iExo STINGa was associated with superior potency compared with STINGa alone in suppressing B16F10 tumor growth. Moreover, iExo STINGa showed superior uptake of STINGa into dendritic cells compared with STINGa alone, which led to increased accumulation of activated CD8 + T-cells and an antitumor immune response. Our study highlights the potential of exosomes in general, and iExo STINGa specifically, in enhancing cancer therapy outcomes.

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“…Further, some concerns remain about the potential tumor growth promoting effects of EVs. Tumor-promoting effects of MSC-derived exosomes were observed by activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, transfer of tumor suppressor miR-15a, miR-410, protection against cell stress, decrease of tumor cell apoptosis, exchange of MMP-2 and ecto-5′ nucleosidase and promotion of angiogenesis [ 70 ]. In addition, the immunomodulatory action of EVs may favor tumor growth.…”

Section: Types Of Mscs and Msc-derived Productsmentioning

confidence: 99%

Therapeutic Potential of Mesenchymal Stem Cells and Their Products in Lung Diseases—Intravenous Administration versus Inhalation

Frőhlich

2021

Pharmaceutics

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The number of publications studying the therapeutic use of stem cells has steadily increased since 2000. Compared to other applications, there has been little interest in the evaluation of mesenchymal stem cells (MSCs) and MSC-derived products (mostly extracellular vesicles) for the treatment of respiratory diseases. Due to the lack of efficient treatments for acute respiratory distress syndrome caused by infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the action of MSCs has also been studied. This review describes mode of action and use of MSCs and MSC-derived products in the treatment of lung diseases including the respective advantages and limitations of the products. Further, issues related to standardized production are addressed. Administration by inhalation of MSCs, compared to intravenous injection, could decrease cell damage by shear stress, eliminate the barrier to reach target cells in the alveoli, prevent thrombus formation in the pulmonary vasculature and retention in filter for extracorporeal membrane oxygenation. There is more feasible to deliver extracellular vesicles than MSCs with inhalers, offering the advantage of non-invasive and repeated administration by the patient. Major obstacles for comparison of results are heterogeneity of the products, differences in the treatment protocols and small study cohorts.

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Biology and therapeutic potential of mesenchymal stem cell‐derived exosomes

Cited by 170 publications

References 121 publications

Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

Effective delivery of STING agonist using exosomes suppresses tumor growth and enhances antitumor immunity

Therapeutic Potential of Mesenchymal Stem Cells and Their Products in Lung Diseases—Intravenous Administration versus Inhalation

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