Extracellular vesicles isolated from adipose tissue-derived mesenchymal stromal cells as carriers for Paclitaxel delivery

Our plain-English summary of Extracellular vesicles isolated from adipose tissue-derived mesenchymal stromal cells as carriers for Paclitaxel delivery, by A. Marcianti, E. Spampinato, S. Nava, et al (Stem Cell Research & Therapy, 2025).

The study

• Authors: A. Marcianti, E. Spampinato, S. Nava, G.M. Stella, P. Perego, S. Pogliani, S. Frigerio, L. Mirra, P. Gagni, F. Moda, F.A. Cazzaniga, G.L. Beretta, G. Maronati, G. Paglia, A.G. Corsico, C. Traversari, D. Lisini
• Journal: Stem Cell Research & Therapy
• Published: 2025;16(1):307
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

BACKGROUND: Mesenchymal Stromal Cells (MSC)-derived Extracellular Vesicles (EV) represent innovative tools for drug delivery systems. However, their clinical use is limited by the lack of standardized good manufacturing practice (GMP)-compliant isolation and conservation protocols. In this study, we developed a GMP-compliant protocol for the preparation of MSC-EVs and investigated the feasibility of producing EVs loaded with paclitaxel (PTX) for clinical application as drug products. METHODS: Adipose tissues from 13 donors were used to obtain MSC-EVs via culture supernatant ultracentrifugation. EVs loaded with PTX were manufactured by adding the drug to the culture medium of MSCs before supernatant collection. EV identity was verified in terms of concentration/size, protein content, morphology, and expression of EV surface markers. The anti-proliferative activity, accumulation ability in tumor cells and PTX content, as well as their stability over time, were also evaluated. RESULTS: High numbers of EV/EV-PTX compliant in terms of integrity/identity were obtained and can be successfully stored for up to one year at -80 °C. Cellular studies have shown that EVs are capable of accumulating in tumor cells and, when loaded with PTX, inhibiting the proliferation of a pleural mesothelioma cell line. CONCLUSIONS: These results support the potential future clinical use of EVs as carriers for drug delivery to improve cancer treatment strategies.

© 2025. The Author(s).

In plain English

This laboratory study tested a way to manufacture extracellular vesicles (EVs), tiny particles released by stromal cells grown from fat tissue donated by 13 healthy adults having cosmetic surgery. Some cells were treated with paclitaxel, a cancer drug, so their vesicles would carry it. No patients were treated and asbestos was not studied. The tests used laboratory mesothelioma cell lines. The vesicles had the expected size and markers and stayed stable for up to 12 months frozen at -80 °C. Labeled vesicles built up in MSTO-211 H mesothelioma cells at the higher of two doses tested. Paclitaxel-loaded vesicles reduced the growth of the pleural mesothelioma cell line NCI H2052 more than unloaded vesicles did (viability 76.0% versus 86.8%). They had less effect than the culture fluid, suggesting most of the drug left the cells in free form. The authors concluded that the results support possible future clinical use of these vesicles as drug carriers. They noted that matching the whole culture fluid's effect would need vesicle numbers that could be hard to produce, and that dosage studies are needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) study developing a GMP-compliant manufacturing protocol for paclitaxel-loaded extracellular vesicles from adipose tissue-derived mesenchymal stromal cells, tested on mesothelioma cell lines
• Who was studied: Adipose tissue lipoaspirates from 13 healthy volunteer donors (9 women, 4 men; mean age 46.4 years, range 20 to 63) undergoing cosmetic plastic surgery, in Italy; mesothelioma cell lines MSTO-211 H and NCI H2052 were used for testing
• Exposure: No asbestos exposure was studied. Stromal cells were treated with paclitaxel (10 µg/mL for 20 to 22 hours) so that their extracellular vesicles would carry the drug
• Main results:
  • From 80 mL of culture fluid, unloaded vesicle preparations yielded a mean of 7.03 ± 6.55 × 10^9 particles, sized 186 to 263 nm. Paclitaxel-loaded preparations yielded 5.92 ± 2.92 × 10^9 particles, sized 189 to 248 nm.
  • Unloaded and paclitaxel-loaded vesicles stored at -80 °C kept their number, size and marker profile for up to 12 months
  • In MSTO-211 H mesothelioma cells, labeled vesicles increased fluorescence at the higher concentration (7.2 × 10^7 EVs, about 5900 EVs per cell). The increase was negligible at the lower concentration.
  • Paclitaxel content was reported as 8.11 ng per 10^6 loaded vesicles (the printed standard deviation is garbled). The vesicle-depleted culture fluid contained 36.18 ± 13.82 ng/mL paclitaxel.
  • In the pleural mesothelioma cell line NCI H2052, paclitaxel-loaded vesicles had a significantly greater effect than unloaded vesicles (paclitaxel equivalent concentration 4.616 versus 3.234 ng/mL; viability 76.0% versus 86.8%; p = 0.02110 for PEC, p = 0.02636 for survival)
  • The isolated paclitaxel-loaded vesicles had a significantly lower effect than the whole culture fluid (viability 26.8%) and the vesicle-depleted culture fluid (viability 32.4%). The authors suggested that most of the paclitaxel was released in free form.
  • Freezing the culture fluid without DMSO for 1 month before isolating the vesicles significantly reduced the MSC markers CD44 (p less than 0.01) and CD29 (p less than 0.05) compared with fresh fluid
  • Comparison with vesicles from platelet lysate medium led the authors to exclude platelet lysate-derived vesicles from the final product
• The authors' conclusion: The authors concluded that the results support the potential future clinical use of these vesicles as carriers for drug delivery in cancer treatment
• Limitations the authors state:
  • To obtain an effect comparable to that of the whole vesicle-containing culture fluid, a number of vesicles would be needed that could be difficult to produce
  • The efficiency of loading paclitaxel into the vesicles was low, possibly because the drug is highly hydrophobic and poorly soluble in water
  • Further studies to determine the optimal dosage are needed before the product can be used in antitumor therapy

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma.

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• Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma — S. Burgio, L. Noori, et al. (2020)
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