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Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
Published on: May 14, 2018
Mesenchymal stromal cells loaded with Paclitaxel (PacliMES) a potential new therapeutic approach on mesothelioma
Valentina Coccè1, Mara Bonelli2, Silvia La Monica2
1CRC StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy.
Abstract:
Malignant pleural mesothelioma is an asbestos-related tumor originating in mesothelial cells of the pleura that poorly responds to chemotherapeutic approaches. Adult mesenchymal stromal cells derived either from bone marrow or from adipose tissue may be considered a good model for cell-based therapy, a treatment which has experienced significant interest in recent years. The present study confirms that Paclitaxel is effective on mesothelioma cell proliferation in 2D and 3D in vitro cultures, and that 80,000 mesenchymal stromal cells loaded with Paclitaxel inhibit tumor growth at a higher extent than Paclitaxel alone. An in vivo approach to treat in situ mesothelioma xenografts using a minimal amount of 106 mesenchymal stromal cells loaded with Paclitaxel showed the same efficacy of a systemic administration of 10 mg/kg of Paclitaxel. These data strongly support drug delivery system by mesenchymal stromal cells as a useful approach against many solid tumors. We look with interest at the favourable opinion recently expressed by the Italian Drug Agency on the procedure for the preparation of mesenchymal stromal cells loaded with Paclitaxel in large-scale bioreactor systems and their storage until clinical use. This new Advanced Medicinal Therapy Product, already approved for a Phase I clinical trial on mesothelioma patients, could pave the way for mesenchymal stromal cells use as drug delivery system on other solid tumors for adjuvant therapy associated with surgery and radiotherapy.
Insights
Mesenchymal stromal cells loaded with Paclitaxel effectively treat mesothelioma. This cell-based drug delivery system shows promise for treating solid tumors, advancing cancer therapy.
Area of Science:
- Oncology
- Cell Biology
- Biomedical Engineering
Background:
- Malignant pleural mesothelioma is an asbestos-related cancer with poor response to chemotherapy.
- Mesenchymal stromal cells (MSCs) are being explored for cell-based therapies.
- Paclitaxel is a chemotherapy agent with activity against mesothelioma cells.
Purpose of the Study:
- To evaluate the efficacy of Paclitaxel-loaded MSCs as a drug delivery system for mesothelioma.
- To compare the anti-tumor effects of Paclitaxel-loaded MSCs with Paclitaxel alone in vitro and in vivo.
- To assess the potential of MSCs as a vehicle for advanced medicinal therapy products.
Main Methods:
- In vitro studies using 2D and 3D mesothelioma cell cultures treated with Paclitaxel and/or MSCs.
- In vivo studies involving mesothelioma xenografts treated with Paclitaxel-loaded MSCs or systemic Paclitaxel.
- Evaluation of tumor growth inhibition and therapeutic efficacy.
Main Results:
- Paclitaxel demonstrated efficacy in inhibiting mesothelioma cell proliferation in vitro.
- MSCs loaded with Paclitaxel showed enhanced inhibition of tumor growth compared to Paclitaxel alone.
- In vivo, MSCs loaded with Paclitaxel achieved comparable efficacy to systemic Paclitaxel administration at a lower dose.
Conclusions:
- Mesenchymal stromal cells serve as an effective drug delivery system for Paclitaxel in mesothelioma treatment.
- This cell-based approach holds significant potential for treating various solid tumors as an adjuvant therapy.
- The development of Paclitaxel-loaded MSCs as an Advanced Medicinal Therapy Product is progressing towards clinical application.
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