CHAPTER 1. Therapeutic Potential of Mesenchymal Stromal Cell-derived Small Extracellular Vesicles

Bauer, Fabiola Nardi; Giebel, Bernd

doi:10.1039/9781839164552-00001

Cited by 3 publications

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“…Much of the controversy around which component of EV payload is biologically active (contributes to MoA) comes from non-standardized EV preparations. The importance of this issue cannot be understated [58][59][60]. The International Society for EVs has established clear criteria for isolating, characterizing, and defining microparticles derived from MSCs [61,62].…”

Section: Msc-ev Contentmentioning

confidence: 99%

The MSC-EV-microRNAome: A Perspective on Therapeutic Mechanisms of Action in Sepsis and ARDS

dos Santos,

Lopes-Pacheco,

English

et al. 2024

Cells

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Mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (EVs) have emerged as innovative therapeutic agents for the treatment of sepsis and acute respiratory distress syndrome (ARDS). Although their potential remains undisputed in pre-clinical models, this has yet to be translated to the clinic. In this review, we focused on the role of microRNAs contained in MSC-derived EVs, the EV microRNAome, and their potential contribution to therapeutic mechanisms of action. The evidence that miRNA transfer in MSC-derived EVs has a role in the overall therapeutic effects is compelling. However, several questions remain regarding how to reconcile the stochiometric issue of the low copy numbers of the miRNAs present in the EV particles, how different miRNAs delivered simultaneously interact with their targets within recipient cells, and the best miRNA or combination of miRNAs to use as therapy, potency markers, and biomarkers of efficacy in the clinic. Here, we offer a molecular genetics and systems biology perspective on the function of EV microRNAs, their contribution to mechanisms of action, and their therapeutic potential.

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Section: Msc-ev Contentmentioning

confidence: 99%

The MSC-EV-microRNAome: A Perspective on Therapeutic Mechanisms of Action in Sepsis and ARDS

dos Santos,

Lopes-Pacheco,

English

et al. 2024

Cells

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Section: Evs As Novel Therapeutics For Covid-19mentioning

confidence: 99%

“…Sengupta et al recently published a human clinical trial on ExoFlo®, a novel therapy involving the administration of bone marrow MSC-EVs (bmMSC-EVs) and reported positive outcomes in moderate-tosevere COVID-19 patients [133] . Following administration of a single 15 mL dose of bmMSC-EVs, ExoFlo® was shown to increase patient survival and reduce the need for invasive oxygen support [133] . Additionally, because bmMSC-EVs have immunomodulatory properties, COVID-19 patients that were given ExoFlo® also demonstrated a significant improvement in immune function and decreased levels of harmful acute inflammation [133] .…”

Section: Evs As Novel Therapeutics For Covid-19mentioning

confidence: 99%

“…Following administration of a single 15 mL dose of bmMSC-EVs, ExoFlo® was shown to increase patient survival and reduce the need for invasive oxygen support [133] . Additionally, because bmMSC-EVs have immunomodulatory properties, COVID-19 patients that were given ExoFlo® also demonstrated a significant improvement in immune function and decreased levels of harmful acute inflammation [133] . Many other clinical trials involving the administration of anti-inflammatory and regenerative MSC-EVs are ongoing and can be found on ClinicalTrials.gov.…”

Section: Evs As Novel Therapeutics For Covid-19mentioning

confidence: 99%

“…For one, the cumulative effects of MSC-EVs are far-reaching. MSC-EVs are most known for their immunomodulatory functions, but they are also shown to affect metabolism, tissue repair mechanisms, and angiogenesis [ 134 ] . Therefore, if administered to patients, the side effects experienced could be highly heterogenous unless MSC-EVs can be tailored to only have specific functions.…”

Section: Evs As Novel Therapeutics For Covid-19mentioning

confidence: 99%

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Exploring extracellular vesicles as mediators of clinical disease and vehicles for viral therapeutics: Insights from the COVID-19 pandemic

Craddock¹,

Cook²,

Dhillon³

2022

Extracell Vesicles Circ Nucleic Acids

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The COVID-19 pandemic has challenged researchers to rapidly understand the capabilities of the SARS-CoV-2 virus and investigate potential therapeutics for SARS-CoV-2 infection. COVID-19 has been associated with devastating lung and cardiac injury, profound inflammation, and a heightened coagulopathic state, which may, in part, be driven by cellular crosstalk facilitated by extracellular vesicles (EVs). In recent years, EVs have emerged as important biomarkers of disease, and while extracellular vesicles may contribute to the spread of COVID-19 infection from one cell to the next, they also may be engineered to play a protective or therapeutic role as decoys or “delivery drivers” for therapeutic agents. This review explores these roles and areas for future study.

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Extracellular vesicles from immortalized mesenchymal stromal cells protect against neonatal hypoxic-ischemic brain injury

et al. 2023

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Background Human mesenchymal stromal cell (MSC)-derived extracellular vesicles (EV) revealed neuroprotective potentials in various brain injury models, including neonatal encephalopathy caused by hypoxia–ischemia (HI). However, for clinical translation of an MSC-EV therapy, scaled manufacturing strategies are required, which is challenging with primary MSCs due to inter- and intra-donor heterogeneities. Therefore, we established a clonally expanded and immortalized human MSC line (ciMSC) and compared the neuroprotective potential of their EVs with EVs from primary MSCs in a murine model of HI-induced brain injury. In vivo activities of ciMSC-EVs were comprehensively characterized according to their proposed multimodal mechanisms of action. Methods Nine-day-old C57BL/6 mice were exposed to HI followed by repetitive intranasal delivery of primary MSC-EVs or ciMSC-EVs 1, 3, and 5 days after HI. Sham-operated animals served as healthy controls. To compare neuroprotective effects of both EV preparations, total and regional brain atrophy was assessed by cresyl-violet-staining 7 days after HI. Immunohistochemistry, western blot, and real-time PCR were performed to investigate neuroinflammatory and regenerative processes. The amount of peripheral inflammatory mediators was evaluated by multiplex analyses in serum samples. Results Intranasal delivery of ciMSC-EVs and primary MSC-EVs comparably protected neonatal mice from HI-induced brain tissue atrophy. Mechanistically, ciMSC-EV application reduced microglia activation and astrogliosis, endothelial activation, and leukocyte infiltration. These effects were associated with a downregulation of the pro-inflammatory cytokine IL-1 beta and an elevated expression of the anti-inflammatory cytokines IL-4 and TGF-beta in the brain, while concentrations of cytokines in the peripheral blood were not affected. ciMSC-EV-mediated anti-inflammatory effects in the brain were accompanied by an increased neural progenitor and endothelial cell proliferation, oligodendrocyte maturation, and neurotrophic growth factor expression. Conclusion Our data demonstrate that ciMSC-EVs conserve neuroprotective effects of primary MSC-EVs via inhibition of neuroinflammation and promotion of neuroregeneration. Since ciMSCs can overcome challenges associated with MSC heterogeneity, they appear as an ideal cell source for the scaled manufacturing of EV-based therapeutics to treat neonatal and possibly also adult brain injury.

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CHAPTER 1. Therapeutic Potential of Mesenchymal Stromal Cell-derived Small Extracellular Vesicles

Cited by 3 publications

References 0 publications

The MSC-EV-microRNAome: A Perspective on Therapeutic Mechanisms of Action in Sepsis and ARDS

The MSC-EV-microRNAome: A Perspective on Therapeutic Mechanisms of Action in Sepsis and ARDS

Exploring extracellular vesicles as mediators of clinical disease and vehicles for viral therapeutics: Insights from the COVID-19 pandemic

Extracellular vesicles from immortalized mesenchymal stromal cells protect against neonatal hypoxic-ischemic brain injury

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