Insights of Extracellular Vesicles of Mesenchymal Stem Cells: a Prospective Cell-Free Regenerative Medicine for Neurodegenerative Disorders

Vatsa, Pankhi; Negi, Renu; Ansari, Uzair Ahmad; Khanna, VK; Pant, Aditya B.

doi:10.1007/s12035-021-02603-7

Cited by 30 publications

(23 citation statements)

References 171 publications

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“…Hence, MSC-derived WT-EVs are considered a safer substitute than their parental cells and carry a complex cargo to exert cellfree effects in recipient cells (33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension

Jiang

Hong²,

Zhu³

et al. 2022

Front. Immunol.

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Extracellular vesicles (EVs) obtain properties of immunomodulation and tissue repair from their parental mesenchymal stem cells (MSCs), and upon delivery may be associated with fewer adverse events. EVs derived from adipose-tissue MSCs restored kidney function by attenuating kidney inflammation in a swine model of metabolic syndrome (MetS) and renal artery stenosis via anti-inflammatory pathways. EVs also ameliorated myocardial injury in renovascular hypertension (RVH) secondary to inflammation in cardiorenal disease, but the mechanisms regulating this effect are unknown. We hypothesize that the anti-inflammatory cytokine interleukin (IL)-10 mediates the reparative effects of EVs on cardiovascular complications in a preclinical swine model with coexisting MetS and RVH. Twenty-three pigs established as Lean controls or RVH models were observed for 16 weeks. At 12 weeks RVH subgroups received an intrarenal delivery of 1011 either wildtype (WT) EVs or EVs after IL-10 knockdown (KD) (RVH+WT-EVs or RVH+IL-10-KD-EVs, respectively). Cardiac and renal function were studied in-vivo and myocardial tissue injury in-vitro 4 weeks later. RVH pigs showed myocardial inflammation, fibrosis, and left ventricular diastolic dysfunction. WT-EVs attenuated these impairments, increased capillary density, and decreased myocardial inflammation in-vivo. In-vitro, co-incubation with IL-10-containing WT-EVs decreased activated T-cells proliferation and endothelial cells inflammation and promoted their migration. Contrarily, these cardioprotective effects were largely blunted using IL-10-KD-EVs. Thus, the anti-inflammatory and pro-angiogenic effects of EVs in RVH may be partly attributed to their cargo of anti-inflammatory IL-10. Early intervention of IL-10-containing EVs may be helpful to prevent cardiovascular complications of MetS concurrent with RVH.

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“…Hence, MSC-derived WT-EVs are considered a safer substitute than their parental cells and carry a complex cargo to exert cellfree effects in recipient cells (33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension

Jiang

Hong²,

Zhu³

et al. 2022

Front. Immunol.

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“…Combinations of this type had been previously hypothesized for BACE-1, however, a few years ago [ 100 ]. At present, the MSC-EVs in various properties [ 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ], in drug delivery [ 91 , 92 ], and in combined employment through a miRNA-BACE-1 axis and various pathways addressed to β-catenin [ 81 , 82 ], have yielded very encouraging results. The new findings concerning MSC-EVs and their therapy agents, considered also in their possible combinations as mentioned here, confirm the improvement of AD therapy, with substantial advantage for the whole population of patients, existing already now and with improvement expected in the next few years.…”

Section: Discussionmentioning

confidence: 99%

“…To be fully comprehensive, however, the results obtained should be analyzed by clinical trials [ 83 , 87 , 88 ]. Due to the paucity of standard protocols and mechanisms available for the procedures, the development of MSC-EV-dependent therapies has been challenged [ 89 , 90 ]. It should be mentioned, however, that some such properties, in particular the drug accumulation within MSC-EVs, have been approved for specific targeting according to recent technical advances [ 91 , 92 ].…”

Section: Present Therapies For Alzheimer’s Diseasementioning

confidence: 99%

News about Therapies of Alzheimer’s Disease: Extracellular Vesicles from Stem Cells Exhibit Advantages Compared to Other Treatments

Meldolesi

2022

Biomedicines

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Upon its discovery, Alzheimer’s, the neurodegenerative disease that affects many millions of patients in the world, remained without an effective therapy. The first drugs, made available near the end of last century, induced some effects, which remained only marginal. More promising effects are now present, induced by two approaches. Blockers of the enzyme BACE-1 induce, in neurons and glial cells, decreased levels of Aβ, the key peptide of the Alzheimer’s disease. If administered at early AD steps, the BACE-1 blockers preclude further development of the disease. However, they have no effect on established, irreversible lesions. The extracellular vesicles secreted by mesenchymal stem cells induce therapy effects analogous, but more convenient, than the effects of their original cells. After their specific fusion to target cells, the action of these vesicles depends on their ensuing release of cargo molecules, such as proteins and many miRNAs, active primarily on the cell cytoplasm. Operationally, these vesicles exhibit numerous advantages: they exclude, by their accurate selection, the heterogeneity of the original cells; exhibit molecular specificity due to their engineering and drug accumulation; and induce effective actions, mediated by variable concentrations of factors and molecules and by activation of signaling cascades. Their strength is reinforced by their combination with various factors and processes. The recent molecular and operations changes, induced especially by the stem cell target cells, result in encouraging and important improvement of the disease. Their further development is expected in the near future.

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“…Regenerative medicine has been widely applied in the research of liver diseases, [ 71 ] neurodegenerative diseases, [ 72 ] colorectal pathologies, [ 73 ] cardiac repair, [ 74 ] tendon healing, [ 75 ] and so on. The key concept of regenerative medicine is to stimulate and support the body’s own self-healing capacity by cell-based biomaterials (cell suspension, cell sheets, ECM scaffold, etc .).…”

Section: Discussionmentioning

confidence: 99%

Advances in the application of regenerative medicine in prevention of post-endoscopic submucosal dissection for esophageal stenosis

Wang

Zhao

Zhang

2022

Journal of Translational Internal Medicine

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Endoscopic submucosal dissection (ESD) is a curative treatment for superficial esophageal cancer with distinct advantages. However, esophageal stenosis after ESD remains a tough problem, especially after large circumferential proportion of esophageal mucosa is removed, which limits the wide use of ESD, especially in circumferential lesions. In this scenario, preventive procedures are highly recommended against post-ESD esophageal stenosis. However, the efficacy and safety of traditional prophylactic methods (steroids, metal and biodegradable stents, balloon dilation, radial incision, etc.) are not satisfactory and novel strategies need to be developed. Regenerative medicine has been showing enormous potential in the reconstruction of organs including the esophagus. In this review, we aimed to describe the current status of regenerative medicine in prevention of post-ESD esophageal stenosis. Cell injection, cell sheet transplantation, and extracellular matrix implantation have been proved effective. However, numerous obstacles still exist and further studies are necessary.

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Insights of Extracellular Vesicles of Mesenchymal Stem Cells: a Prospective Cell-Free Regenerative Medicine for Neurodegenerative Disorders

Cited by 30 publications

References 171 publications

IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension

IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension

News about Therapies of Alzheimer’s Disease: Extracellular Vesicles from Stem Cells Exhibit Advantages Compared to Other Treatments

Advances in the application of regenerative medicine in prevention of post-endoscopic submucosal dissection for esophageal stenosis

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