Exosomes Secreted by the Cocultures of Normal and Oxygen–Glucose-Deprived Stem Cells Improve Post-stroke Outcome

Nalamolu, Koteswara Rao; Venkatesh, Ishwarya; Mohandass, Adithya; Klopfenstein, Jeffrey D.; Pinson, David M.; Wang, David Z.; Kunamneni, Adinarayana; Veeravalli, Krishna Kumar

doi:10.1007/s12017-019-08540-y

Cited by 42 publications

(25 citation statements)

References 39 publications

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“…Li et al reported that small noncytotoxic pharmacological molecules, including MOPIPP and vacuolin-1, promote the production of exosomes and can be used to treat GBM [ 138 ]. Other current challenges associated with exosome-based treatment are donor-cell selection, drug encasement into exosomes, and drug resistance [ 14 ]. Therefore, miRNAs can be efficacious treatment agents for multiple diseases, and for the delivery of different synthetic molecules and biomolecules in cell therapy.…”

Section: Exosomes In the Treatment Of Gliomasmentioning

confidence: 99%

“…The contents of some exosomes are similar, whereas exosomes from different subclasses specialize in specific biological functions [ 13 ]. As exosomes are rich and diverse in their biomolecular contents, can be obtained by minimally invasive techniques, and monitored dynamically, the detection of exosomes and their contents in the peripheral fluids (including blood and cerebrospinal fluid) of patients is an efficient way to diagnose tumors using a fluid biopsy [ 14 ]. Tumor cells secrete more exosomes than normal cells [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…As exosomes are rich and diverse in their biomolecular contents, can be obtained by minimally invasive techniques, and monitored dynamically, the detection of exosomes and their contents in the peripheral fluids (including blood and cerebrospinal fluid) of patients is an efficient way to diagnose tumors using a fluid biopsy [ 14 ]. Tumor cells secrete more exosomes than normal cells [ 14 ]. Recent studies have revealed that exosomes bind to receptors on the surfaces of target tumor cells via surface markers [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Role of Exosomes in the Progression, Diagnosis, and Treatment of Gliomas

et al. 2020

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Gliomas are the most common primary malignant brain tumors associated with a low survival rate. Even after surgery, radiotherapy, and chemotherapy, gliomas still have a poor prognosis. Extracellular vesicles are a heterogeneous group of cell-derived membranous structures. Exosomes are a type of extracellular vesicles, their size ranges from 30 nm to 100 nm. Recent studies have proved that glioma cells could release numerous exosomes; therefore, exosomes have gained increasing attention in glioma-related research. Recent studies have confirmed the importance of extracellular vesicles, particularly exosomes, in the development of brain tumors, including gliomas. Exosomes mediate intercellular communication in the tumor microenvironment by transporting biomolecules (proteins, lipids, deoxyribonucleic acid, and ribonucleic acid); thereby playing a prominent role in tumor proliferation, differentiation, metastasis, and resistance to chemotherapy or radiation. Given their nanoscale size, exosomes can traverse the blood-brain barrier and promote tumor progression by modifying the tumor microenvironment. Based on their structural and functional characteristics, exosomes are demonstrating their value not only as diagnostic and prognostic markers, but also as tools in therapies specifically targeting glioma cells. Therefore, exosomes are a promising therapeutic target for the diagnosis, prognosis, and treatment of malignant gliomas. More research will be needed before exosomes can be used in clinical applications. Here, we describe the exosomes, their morphology, and their roles in the diagnosis and progression of gliomas. In addition, we discuss the potential of exosomes as a therapeutic target/drug delivery system for patients with gliomas.

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Section: Exosomes In the Treatment Of Gliomasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of Exosomes in the Progression, Diagnosis, and Treatment of Gliomas

et al. 2020

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“…All these studies were published between 2013 and 2020, and 367 animals were included in this meta-analysis. Among the included studies, six of them used bone marrow mesenchymal stromal cells-exosome (Xin et al, 2013a(Xin et al, , 2017aDeng et al, 2019;Safakheil and Safakheil, 2020;Zhao et al, 2020), one adopted adipose-derived mesenchymal stem cells-exosome (Chen K. H. et al, 2016), one applied human umbilical cord mesenchymal stem cells-exosome , one used human umbilical cord blood mesenchymal stromal cells-exosome (Nalamolu et al, 2019b), one used adipose-derived stem cellsexosome (Jiang et al, 2018), one used neural stem cells-exosome (Sun et al, 2019), one used human urine-derived stem cellsexosome (Ling et al, 2020), one used mouse brain endothelial cells-exosome (Venkat et al, 2019), one used macrophagesexosome (Zheng et al, 2019), one used microglia-exosome, and one used astrocytes-exosome (Pei et al, 2019;Song et al, 2019), and the two remaining used another origin of exosomes (Li et al, 2019;Nalamolu et al, 2019a). The ischemic stroke model was established with a unifilar nylon suture (Xin et al, 2013a(Xin et al, , 2017aChen K. H. et al, 2016;Jiang et al, 2018;Deng et al, 2019;Nalamolu et al, 2019a,b;Pei et al, 2019;Song et al, 2019;Sun et al, 2019;Zheng et al, 2019;Ling et al, 2020;Safakheil and Safakheil, 2020;Zhao et al, 2020), bipolar electrocoagulation forceps (Li et al, 2019), or thrombus (Venkat et al, 2019).…”

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

Effects of Exosomes on Neurological Function Recovery for Ischemic Stroke in Pre-clinical Studies: A Meta-analysis

Huang

Hong

Xiao

et al. 2020

Front. Cell. Neurosci.

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Background: Exosomes, especially stem cell-derived exosomes, have been widely studied in pre-clinical research of ischemic stroke. However, their pooled effects remain inconclusive.Methods: Relevant literature concerning the effects of exosomes on neurological performance in a rodent model of ischemic stroke was identified via searching electronic databases, including PubMed, Embase, and Web of Science. The primary outcomes included neurological function scores (NFS) and infarct volume (IV), and the secondary outcomes were several pro-inflammatory factors and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling-positive cells. Subgroup analyses regarding several factors potentially influencing the effects of exosomes on NFS and IV were also conducted.Results: We identified 21 experiments from 18 studies in the meta-analysis. Pooled analyses showed the positive and significant effects of exosomes on NFS (standardized mean difference −2.79; 95% confidence interval −3.81 to −1.76) and IV (standardized mean difference −3.16; 95% confidence interval −4.18 to −2.15). Our data revealed that the effects of exosomes on neurological outcomes in rodent stroke models might be related to routes of administration and exosomes sources. In addition, there was significant attenuation in pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and interleukin-1β, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling-positive cells when undergoing exosomes treatment.Conclusion: Cell-derived exosomes treatment demonstrated statistically significant improvements in structural and neurological function recovery in animal models of ischemic stroke. Our results also provide relatively robust evidence supporting cell-derived exosomes as a promising therapy to promote neurological recovery in stroke individuals.

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“…However, motor functions on the mNSS, modified adhesive removal test, beam walking, and accelerating rotarod performance test were exacerbated after stroke in exosome-treated rats [ 39 ]. Subsequently, they conducted another study using the same rat stroke model and showed that exosomes derived from the combination of normal and hypoxic MSCs significantly improved motor function on such tests [ 40 ]. It was suggested that differences in the type and expression levels of proteins and microRNAs in the exosomes from the combination of normal and hypoxic HUCB-MSCs could have contributed to the therapeutic benefit.…”

Section: Therapeutic Effect Of Exosomes For Stroke Recoverymentioning

confidence: 99%

Pleiotropic Effects of Exosomes as a Therapy for Stroke Recovery

Ueno

Hira

Miyamoto

et al. 2020

IJMS

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Stroke is the leading cause of disability, and stroke survivors suffer from long-term sequelae even after receiving recombinant tissue plasminogen activator therapy and endovascular intracranial thrombectomy. Increasing evidence suggests that exosomes, nano-sized extracellular membrane vesicles, enhance neurogenesis, angiogenesis, and axonal outgrowth, all the while suppressing inflammatory reactions, thereby enhancing functional recovery after stroke. A systematic literature review to study the association of stroke recovery with exosome therapy was carried out, analyzing species, stroke model, source of exosomes, behavioral analyses, and outcome data, as well as molecular mechanisms. Thirteen studies were included in the present systematic review. In the majority of studies, exosomes derived from mesenchymal stromal cells or stem cells were administered intravenously within 24 h after transient middle cerebral artery occlusion, showing a significant improvement of neurological severity and motor functions. Specific microRNAs and molecules were identified by mechanistic investigations, and their amplification was shown to further enhance therapeutic effects, including neurogenesis, angiogenesis, axonal outgrowth, and synaptogenesis. Overall, this review addresses the current advances in exosome therapy for stroke recovery in preclinical studies, which can hopefully be preparatory steps for the future development of clinical trials involving stroke survivors to improve functional outcomes.

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Exosomes Secreted by the Cocultures of Normal and Oxygen–Glucose-Deprived Stem Cells Improve Post-stroke Outcome

Cited by 42 publications

References 39 publications

Role of Exosomes in the Progression, Diagnosis, and Treatment of Gliomas

Role of Exosomes in the Progression, Diagnosis, and Treatment of Gliomas

Effects of Exosomes on Neurological Function Recovery for Ischemic Stroke in Pre-clinical Studies: A Meta-analysis

Pleiotropic Effects of Exosomes as a Therapy for Stroke Recovery

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