Enhancing EV-cell communication through "External Modulation of Cell by EV" (EMCEV).

Mesenchymal stem/stromal cells (MSC) have displayed promising therapeutic potential. Nonetheless, no United States Food and Drug Administration (FDA)-approved MSC product exists due largely to the absence of a reliable potency assay based on the mechanisms of action to ensure consistent efficacy. MSCs are now thought to exert their effects primarily by releasing small extracellular vesicles (sEVs) of 50-200 nm.

An Assessment of Administration Route on MSC-sEV Therapeutic Efficacy.

Mesenchymal stem/stromal cell-derived small extracellular vesicles (MSC-sEVs) are promising therapeutic agents. In this study, we investigated how the administration route of MSC-sEVs affects their therapeutic efficacy in a mouse model of bleomycin (BLM)-induced skin scleroderma (SSc). We evaluated the impact of topical (TOP), subcutaneous (SC), and intraperitoneal (IP) administration of MSC-sEVs on dermal fibrosis, collagen density, and thickness.

Standard Radio-Iodine Labeling Protocols Impaired the Functional Integrity of Mesenchymal Stem/Stromal Cell Exosomes.

Mesenchymal stem/stromal cells (MSCs) are an extensively studied cell type in clinical trials due to their easy availability, substantial ex vivo proliferative capacity, and therapeutic efficacy in numerous pre-clinical animal models of disease. The prevailing understanding suggests that their therapeutic impact is mediated by the secretion of exosomes. Notably, MSC exosomes present several advantages over MSCs as therapeutic agents, due to their non-living nature and smaller size.

Engineered EVs with pathogen proteins: promising vaccine alternatives to LNP-mRNA vaccines.

Extracellular vesicles (EVs) are tiny, lipid membrane-bound structures that are released by most cells. They play a vital role in facilitating intercellular communication by delivering bioactive cargoes to recipient cells and triggering cellular as well as biological responses. EVs have enormous potential for therapeutic applications as native or engineered exosomes.

Therapeutic Efficacy of Mesenchymal Stem/Stromal Cell Small Extracellular Vesicles in Alleviating Arthritic Progression by Restoring Macrophage Balance.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and damage, often associated with an imbalance in M1/M2 macrophages. Elevated levels of anti-inflammatory M2 macrophages have been linked to a therapeutic response in RA. We have previously demonstrated that mesenchymal stem/stromal cell small extracellular vesicles (MSC-sEVs) promote M2 polarization and hypothesized that MSC-sEVs could alleviate RA severity with a concomitant increase in M2 polarization.

MSC-sEV Treatment Polarizes Pro-Fibrotic M2 Macrophages without Exacerbating Liver Fibrosis in NASH.

Mesenchymal stem/stromal cell small extracellular vesicles (MSC-sEVs) have shown promise in treating a wide range of animal models of various human diseases, which has led to their consideration for clinical translation. However, the possibility of contraindication for MSC-sEV use is an important consideration. One concern is that MSC-sEVs have been shown to induce M2 macrophage polarization, which is known to be pro-fibrotic, potentially indicating contraindication in fibrotic diseases such as liver fibrosis.

A roadmap from research to clinical testing of mesenchymal stromal cell exosomes in the treatment of psoriasis.

The most clinically trialed cells, mesenchymal stromal cells (MSCs), are now known to mainly exert their therapeutic activity through paracrine secretions, which include exosomes. To mitigate potential regulatory concerns on the scalability and reproducibility in the preparations of MSC exosomes, MSC exosomes were produced using a highly characterized MYC-immortalized monoclonal cell line. These cells do not form tumors in athymic nude mice or exhibit anchorage-independent growth, and their exosomes do not carry MYC protein or promote tumor growth.

Assessment of Tumorigenic Potential in Mesenchymal-Stem/Stromal-Cell-Derived Small Extracellular Vesicles (MSC-sEV).

Mesenchymal-stem/stromal-cell-derived small extracellular vesicles (MSC-sEV) have been shown to ameliorate many diseases in preclinical studies. However, translating MSC-sEV into clinical use requires the development of scalable manufacturing processes for highly reproducible preparations of safe and potent MSC-sEVs. A major source of variability in MSC-sEV preparations is EV producer cells.

Topical Application of Mesenchymal Stem Cell Exosomes Alleviates the Imiquimod Induced Psoriasis-Like Inflammation.

Severe psoriasis, a chronic inflammatory skin disease is increasingly being effectively managed by targeted immunotherapy but long-term immunotherapy poses health risk and loss of response. Therefore, there is a need for alternative therapy strategies. Mesenchymal stem/stromal cell (MSC) exosomes are widely known for their potent immunomodulatory properties.

Extracellular vesicles yield predictive pre-eclampsia biomarkers.

Circulating extracellular vesicles (EVs) such as cholera toxin B chain (CTB)- or annexin V (AV)-binding EVs were previously shown to be rich sources of biomarkers. Here we test if previously identified pre-eclampsia (PE) candidate biomarkers, TIMP-1 in CTB-EVs (CTB-TIMP) and PAI-1 in AV-EVs (AV-PAI) complement plasma PlGF in predicting PE in a low-risk obstetric population. Eight hundred and forty-three prospectively banked plasma samples collected at 28 + 0 to 32 + 0 gestation weeks in the Neonatal and Obstetrics Risk Assessment (NORA) cohort study were assayed by sandwich ELISAs for plasma PlGF, CTB-TIMP1 and AV-PAI1.