Label‐free characterization of an extracellular vesicle‐based therapeutic

Priglinger, Eleni; Strasser, Jürgen; Buchroithner, Boris; Weber, Florian; Wolbank, Susanne; Auer, Daniela; Grasmann, Eva; Arzt, Claudia; Sivun, Dmitry; Grillari, Johannes; Jacak, Jaroslaw; Preiner, Johannes; Gimona, Mario

doi:10.1002/jev2.12156

Cited by 25 publications

(35 citation statements)

References 58 publications

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“…In the osteoimmunology microenvironment, MSCs are characterized by a fibroblast-like morphology that can differentiate into a variety of cell types, including osteoblastic lineage cells 30 . Subcluster 2, which was annotated as CD55 + MSCs, also expressed other classical MSC markers, NT5E 31 - 33 and LepR 34 , 35 ( Figure S3 A). We next used flow cytometry sorting to isolate CD55 + NT5E + LepR + or CD45 - CD55 + cells from human periodontal tissues of clinically healthy donors.…”

Section: Resultsmentioning

confidence: 99%

Single-cell RNA landscape of the osteoimmunology microenvironment in periodontitis

Chen¹,

Wang²,

Yang³

et al. 2022

Theranostics

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Single-cell RNA sequencing (scRNA-seq) enables specific profiling of cell populations at single-cell resolution. The osteoimmunology microenvironment in the occurrence and development of periodontitis remains poorly understood at the single-cell level. In this study, we used single-cell transcriptomics to comprehensively reveal the complexities of the molecular components and differences with counterparts residing in periodontal tissues. Methods: We performed scRNA-seq to identify 51248 single cells from healthy controls (n=4), patients with severe chronic periodontitis (n=5), and patients with severe chronic periodontitis after initial periodontal therapy within 1 month (n=3). Uniform manifold approximation and projection (UMAP) were further conducted to explore the cellular composition of periodontal tissues. Pseudotime cell trajectory and RNA velocity analysis, combined with gene enrichment analysis were used to reveal the molecular pathways underlying cell fate decisions. CellPhoneDB were performed to identify ligand-receptor pairs among the major cell types in the osteoimmunology microenvironment of periodontal tissues. Results: A cell atlas of the osteoimmunology microenvironment in periodontal tissues was characterized and included ten major cell types, such as fibroblasts, monocytic cells, endothelial cells, and T and B cells. The enrichment of TNFRSF21 + fibroblasts with high expression of CXCL1, CXCL2, CXCL5, CXCL6, CXCL13 , and IL24 was detected in patients with periodontitis compared to healthy individuals. The fractions of CD55 + mesenchymal stem cells (MSCs), APOE + pre-osteoblasts (pre-OBs), and IBSP + osteoblasts decreased significantly in response to initial periodontal therapy. In addition, CXCL12 + MSC-like pericytes could convert their identity into a pre-OB state during inflammatory responses even after initial periodontal therapy confirmed by single-cell trajectory. Moreover, we portrayed the distinct subtypes of monocytic cells and abundant endothelial cells significantly involved in the immune response. The heterogeneity of T and B cells in periodontal tissues was characterized. Finally, we mapped osteoblast/osteoclast differentiation mediators to their source cell populations by identifying ligand-receptor pairs and highlighted the effects of Ephrin-Eph signaling on bone regeneration after initial periodontal therapy. Conclusions: Our analyses uncovered striking spatiotemporal dynamics in gene expression, population composition, and cell-cell interactions during periodontitis progression. These findings provide insights into the cellular and molecular underpinning of periodontal bone regeneration.

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Section: Resultsmentioning

confidence: 99%

Single-cell RNA landscape of the osteoimmunology microenvironment in periodontitis

Chen¹,

Wang²,

Yang³

et al. 2022

Theranostics

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“…Knowledge over the active components of UC-MSC-EVs remains still partial, but the immunomodulatory effects of EVs appear to be relevant to the therapeutic impact. Adenosine signaling may contribute to the immunomodulatory activity of EVs via the conversion of AMP to adenosine by the GPI-anchored 5′-ecto-nucleotidase CD73 present on enriched UC-MSC EVs (Priglinger et al, 2021 ). A recent report by Zhai et al ( 2021 ) demonstrated that the use of EVs produced by virus-transformed hUC-MSC engineered to increase the levels of CD73 alleviated inflammation after SCI in a mouse model, and regulated macrophage polarization in vitro .…”

Section: Discussionmentioning

confidence: 99%

Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury

Romanelli

Bieler

Heimel

et al. 2022

Front. Cell. Neurosci.

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Local inflammation plays a pivotal role in the process of secondary damage after spinal cord injury. We recently reported that acute intravenous application of extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stromal cells dampens the induction of inflammatory processes following traumatic spinal cord injury. However, systemic application of EVs is associated with delayed delivery to the site of injury and the necessity for high doses to reach therapeutic levels locally. To resolve these two constraints, we injected EVs directly at the lesion site acutely after spinal cord injury. We report here that intralesional application of EVs resulted in a more robust improvement of motor recovery, assessed with the BBB score and sub-score, as compared to the intravenous delivery. Moreover, the intralesional application was more potent in reducing inflammation and scarring after spinal cord injury than intravenous administration. Hence, the development of EV-based therapy for spinal cord injury should aim at an early application of vesicles close to the lesion.

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“…Although CD63 generally used as a surface marker to identify EVs [40], there are also reports about different miRNA cargos in CD63-positive EVs in comparison to CD47positive EVs, such as those with potentially different functions [41].…”

Section: Discussionmentioning

confidence: 99%

Repetitive Treatment with Volatile Anesthetics Does Not Affect the In Vivo Plasma Concentration and Composition of Extracellular Vesicles in Rats

Berne

Beckers

Theißen

et al. 2021

CIMB

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Background: Anesthetic-induced preconditioning (AIP) with volatile anesthetics is a well-known experimental technique to protect tissues from ischemic injury or oxidative stress. Additionally, plasmatic extracellular vesicle (EV) populations and their cargo are known to be affected by AIP in vitro, and to provide organ protective properties via their cargo. We investigated whether AIP would affect the generation of EVs in an in vivo rat model. Methods: Twenty male Sprague Dawley rats received a repetitive treatment with either isoflurane or with sevoflurane for a duration of 4 or 8 weeks. EVs from blood plasma were characterized by nanoparticle tracking analysis, transmission electron microscopy (TEM) and Western blot. A scratch assay (H9C2 cardiomyoblast cell line) was performed to investigate the protective capabilities of the isolated EVs. Results: TEM images as well as Western blot analysis indicated that EVs were successfully isolated. The AIP changed the flotillin and CD63 expression on the EV surface, but not the EV concentration. The scratch assay did not show increased cell migration and/or proliferation after EV treatment. Conclusion: AIP in rats changed the cargo of EVs but had no effect on EV concentration or cell migration/proliferation. Future studies are needed to investigate the cargo on a miRNA level and to investigate the properties of these EVs in additional functional experiments.

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Label‐free characterization of an extracellular vesicle‐based therapeutic

Cited by 25 publications

References 58 publications

Single-cell RNA landscape of the osteoimmunology microenvironment in periodontitis

Single-cell RNA landscape of the osteoimmunology microenvironment in periodontitis

Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury

Repetitive Treatment with Volatile Anesthetics Does Not Affect the In Vivo Plasma Concentration and Composition of Extracellular Vesicles in Rats

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