Related Experiment Video

Updated: Mar 5, 2026

Isolation, Characterization, and Therapeutic Application of Extracellular Vesicles from Cultured Human Mesenchymal Stem Cells
07:03

Isolation, Characterization, and Therapeutic Application of Extracellular Vesicles from Cultured Human Mesenchymal Stem Cells

Published on: September 23, 2022

2.7K

TRAIL delivery by MSC-derived extracellular vesicles is an effective anticancer therapy

ZhengQiang Yuan1, Krishna K Kolluri1, Kate H C Gowers1

  • 1Lungs for Living Research Centre, UCL Respiratory, Division of Medicine, University College London , London , UK.

Journal of Extracellular Vesicles
|March 23, 2017
PubMed

Insights

Mesenchymal stromal cell-derived extracellular vesicles (EVs) carrying TNF-related apoptosis-inducing ligand (TRAIL) effectively kill cancer cells. This novel EV-mediated drug delivery overcomes TRAIL resistance and enhances cancer therapy.

Area of Science:

  • Biotechnology
  • Cell Biology
  • Cancer Research

Background:

  • Extracellular vesicles (EVs) are nanoparticles mediating intercellular communication and hold promise for drug delivery.
  • TNF-related apoptosis-inducing ligand (TRAIL) induces cancer cell apoptosis but faces clinical challenges like low bioavailability and resistance.
  • Mesenchymal stromal cells (MSCs) are a potential source for therapeutic EV production.

Purpose of the Study:

  • To investigate the expression of TRAIL in MSC-derived EVs.
  • To evaluate the anticancer efficacy of TRAIL-expressing EVs (MSCT-EVs).
  • To explore strategies for enhancing MSCT-EVs' therapeutic potential.

Main Methods:

  • EVs were isolated from MSCs and TRAIL-expressing MSCs (MSCTs) using ultracentrifugation.
  • EV characterization included size analysis (50-70 nm) and surface marker analysis (CD63, CD9, CD81, surface TRAIL).
  • Cytotoxicity assays were performed on 11 cancer cell lines and primary bronchial epithelial cells, with mechanistic studies involving caspase inhibition and TRAIL neutralization.

Main Results:

  • MSCT-EVs successfully expressed surface TRAIL, confirmed by marker analysis.
  • MSCT-EVs demonstrated dose-dependent apoptosis induction in 11 cancer cell lines without harming normal cells.
  • TRAIL-positive EV cytotoxicity was blocked by caspase inhibition or TRAIL neutralization, confirming the mechanism.
  • MSCT-EVs effectively induced apoptosis in TRAIL-resistant cancer cells, with enhanced efficacy upon CDK9 inhibitor treatment.

Conclusions:

  • TRAIL delivery via MSC-derived EVs represents a viable and effective anticancer therapeutic strategy.
  • EV-mediated TRAIL delivery overcomes limitations associated with recombinant TRAIL, including cancer cell resistance.
  • Combining MSCT-EVs with agents like CDK9 inhibitors may further potentiate their anticancer activity.
Keywords:
EVMSCTRAILcancer

More Related Videos

A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells11:15

A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells

Published on: May 6, 2018

10.7K
Setting a Successful Sorting for Extracellular Vesicle Isolation08:37

Setting a Successful Sorting for Extracellular Vesicle Isolation

Published on: October 11, 2024

1.8K

Related Concept Videos

Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
5.7K
Overview of Exosomes01:36

Overview of Exosomes

Exosomes are stable, lipid bilayer-enclosed vesicles capable of crossing biological barriers. They can carry a wide range of molecules required for intercellular communication. Once exosomes are released from the cell where they originated, they enter a recipient cell through various pathways such as fusion, receptor-mediated endocytosis, macropinocytosis, and phagocytosis.
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
3.8K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
6.2K
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
6.7K