Exosomes derived from human neural stem cells stimulated by interferon gamma improve therapeutic ability in ischemic stroke model

Zhang, Guilong; Zhu, Zhihan; Wang, Hong; Yu, Yongbo; Chen, Wanghao; Waqas, Ahmed; Wang, Yezhong; Chen, Lukui

doi:10.1016/j.jare.2020.05.017

Cited by 63 publications

(47 citation statements)

References 38 publications

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“…MSC‐EVs can mediate the therapeutic effects of MSCs and affect the immune response, inflammation, cell proliferation, and metabolism (Xie et al, 2020). The quality and therapeutic function of MSCs‐EVs is promoted by factors such as hypoxia preconditioning of BM‐MSCs and stimulation with IFN‐γ (Ren et al, 2019; Zhang et al, 2020). The results of in vitro studies show that hypoxic preconditioning of MSCs generates distinctive changes in stem cell characteristics and influences the secretion of various cytokines and growth factors.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that that hypoxia can stimulate cells to release more EVs, and change the EVs cargoes, which include selective proteins and miRNAs (Duan et al, 2019). The quality and therapeutic function of MSCs‐EVs is promoted by factors such as hypoxic preconditioning of BM‐MSCs and stimulation with IFN‐γ (Ren et al, 2019; Zhang et al, 2020). In some hypoxic studies, MSC‐EVs derived from hypoxic conditions had a therapeutic and protective effect via multifunctional processes that involve negative regulation of the apoptotic process, downregulation of oxidative stress, promotion of angiogenesis, and antifibrotic mechanisms (Duan et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal stem cell‐derived extracellular vesicles conditionally ameliorate bone marrow failure symptoms in an immune‐mediated aplastic anemia mouse model

Gholampour

Abroun

Nieuwland

et al. 2021

Journal Cellular Physiology

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Acquired forms of Aplastic anemia (AA) are characterized by T cell‐mediated immune disease resulting in bone marrow (BM) failure and marrow hypoplasia. In these cases, it is a major challenge to modulate autoreactive T cell activity and thereby decrease the pro‐inflammatory cytokine storm. Emerging evidence indicates that extracellular vesicles derived from mesenchymal stem cells (MSC‐EVs) control and modulate immunity. The therapeutic potential of MSC‐EVs has not been investigated in acquired AA. Hence, in this study, we constructed an AA mice model through irradiation and splenocyte infusion to test the benefits of hypoxic MSC‐EVs (Hx‐EVs) and normoxic MSC‐EVs (Nx‐EVs). We found that MSC‐EVs treatment significantly prolonged the survival rate and increased the platelet (PLT) counts of the AA mice. Immunohistochemical staining and colony assay confirmed amelioration of hypoplasia in the BM and increased numbers of hematopoietic stem cells (HSCs). These effects of MSC‐EVs were mediated by T cell suppression and inhibition of interferon‐gamma (IFN‐γ) and tumor necrosis factor‐alpha (TNF‐α) production in the AA mouse model. In addition, an in vitro study revealed that MSC‐EVs led to reduced IFN‐γ and TNF‐α levels and there was an association with decreased splenocyte viability. Previous studies examined the diagnostic and prognostic values of microRNAs (miRNAs) in AA and identified miR‐199a, miR‐146a, miR‐223, and miR‐126. We used quantitative real‐time PCR to evaluate the expression of these miRNAs on isolated BM mononuclear cells (BM‐MNCs) from treated and untreated AA mice. miR‐223, miR‐146a, and miR‐199a expressions increased in the MSC‐EVs treated AA mice. Treatment with MSC‐EVs increased expression of miR‐223 and miR‐146a. Our findings showed that treatment with MSC‐EVs significantly ameliorated immune destruction of HSCs in the AA mouse model and confirmed the importance of miRNAs in the clinical status of this model.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell‐derived extracellular vesicles conditionally ameliorate bone marrow failure symptoms in an immune‐mediated aplastic anemia mouse model

Gholampour

Abroun

Nieuwland

et al. 2021

Journal Cellular Physiology

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“…SVZ NSCs obtained from the human fetal brain tissue were kept in our laboratory (approved by the Institutional Review Board of Zhongda Hospital Southeast University), as previously described[ 19 - 21 ]. NSCs were cultured in serum-free DMEM/F12 medium (Gibco) supplemented with 2% B27 (Gibco), 20 ng/mL basic FGF (bFGF, PeproTech), 20 ng/mL EGF (PeproTech), 2 nmol/L L-glutamine (Invitrogen), 2 μg/mL heparin sodium, and 1% penicillin-streptomycin (Gibco), and incubated at 37 °C in an incubator containing 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Effect of conditioned medium from neural stem cells on glioma progression and its protein expression profile analysis

Zhang¹,

Cheng²,

Zhang³

et al. 2020

WJSC

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BACKGROUND Emerging evidence suggests that the spread of glioma to the subventricular zone (SVZ) is closely related to glioma recurrence and patient survival. Neural stem cells (NSCs) are the main cell type in the SVZ region and exhibit tumor-homing ability. AIM To evaluate the effects of conditioned medium (CM) derived from SVZ NSCs on the cancer-related behaviors of glioma cells. METHODS The characteristics of SVZ hNSCs were identified by immunofluorescence. The normoxic-hNSC-CM and hypoxic-hNSC-CM (3% O 2 , oxygen-glucose deprived [OGD] culturing) were collected from 80%-90% confluent SVZ NSCs in sterile conditions. The CCK8 and Transwell assays were used to compare and evaluate the effects of normoxic-CM and hypoxic-CM on glioma proliferation and invasion. Then proteins secreted from SVZ NSCs into the CM were investigated by mass spectrometry, and the potential effects of candidate protein NCAN in the regulation of glioma progression were examined by CCK8 and Transwell assays. RESULTS The CM from SVZ NSCs significantly increased the proliferation and invasion of glioma cells, particularly the CM from OGD NSCs induced under hypoxic conditions. Furthermore, the secreted protein neurocan (NCAN) in CM from OGD NSCs was identified by proteomic analysis. NCAN was expressed in glioma cells and played regulatory roles in mediating the progression of glioma cells mainly via the Rho/Rho-associated protein kinase pathway. CONCLUSION Our study identified a potential interactive mechanism between SVZ NSCs and glioma cells, in which SVZ NSCs promote glioma progression via the secreted protein NCAN. These findings suggested that exploring the CM derived from cells could be a novel strategy for optimizing treatments and that NCAN derived from SVZ NSCs may be a potential new target in glioma progression.

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“…A study compared the role of exosomes derived from interferon gamma (IFN-γ)-stimulating stem cells and control exosomes for treating ischemic stroke and found that IFN-γ preconditioning did not affect the secretion, but significantly altered the functional abilities of exosomes. Moreover, IFN-γ exosomes increased cell proliferation and cell survival as well as decreased cell apoptosis in vitro while exerting therapeutic effects in vivo in an ischemic rat model ( Zhang G. et al, 2020 ). IFN-γ-exosomes have been used for treating neurodegenerative disorders, i.e., multiple sclerosis.…”

Section: Bioengineering Of Exosomes For Brain Targetingmentioning

confidence: 99%

Native and Bioengineered Exosomes for Ischemic Stroke Therapy

Khan

Pan

et al. 2021

Front. Cell Dev. Biol.

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Exosomes are natural cells-derived vesicles, which are at the forefront toward clinical success for various diseases, including cerebral ischemia. Exosomes mediate cell-to-cell communication in different brain cells during both physiological and pathological conditions. Exosomes are an extensively studied type of extracellular vesicle, which are considered to be the best alternative for stem cell–based therapy. They can be secreted by various cell types and have unique biological properties. Even though native exosomes have potential for ischemic stroke therapy, some undesirable features prevent their success in clinical applications, including a short half-life, poor targeting property, low concentration at the target site, rapid clearance from the lesion region, and inefficient payload. In this review, we highlight exosome trafficking and cellular uptake and survey the latest discoveries in the context of exosome research as the best fit for brain targeting owing to its natural brain-homing abilities. Furthermore, we overview the methods by which researchers have bioengineered exosomes (BioEng-Exo) for stroke therapy. Finally, we summarize studies in which exosomes were bioengineered by a third party for stroke recovery. This review provides up-to-date knowledge about the versatile nature of exosomes with a special focus on BioEng-Exo for ischemic stroke. Standard exosome bioengineering techniques are mandatory for the future and will lead exosomes toward clinical success for stroke therapy.

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Exosomes derived from human neural stem cells stimulated by interferon gamma improve therapeutic ability in ischemic stroke model

Cited by 63 publications

References 38 publications

Mesenchymal stem cell‐derived extracellular vesicles conditionally ameliorate bone marrow failure symptoms in an immune‐mediated aplastic anemia mouse model

Mesenchymal stem cell‐derived extracellular vesicles conditionally ameliorate bone marrow failure symptoms in an immune‐mediated aplastic anemia mouse model

Effect of conditioned medium from neural stem cells on glioma progression and its protein expression profile analysis

Native and Bioengineered Exosomes for Ischemic Stroke Therapy

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