Human skin-derived fibroblasts used as a 'Trojan horse' for drug delivery
| Autor: | A. Vitale, C. A. M. La Porta, Emilio Ciusani, Valentina Coccè, Augusto Pessina, Maura Brambilla, Eugenio Parati, Arianna Bonomi, S. Colombo, Paolo Brambilla, Francesca Sisto, Giulio Alessandri |
|---|---|
| Přispěvatelé: | Coccè, V, Vitale, A, Colombo, S, Bonomi, A, Sisto, F, Ciusani, E, Alessandri, G, Parati, E, Brambilla, P, Brambilla, M, La Porta, C, Pessina, A |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA Stromal cell Paclitaxel Dermatology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Delivery Systems Cell Line Tumor medicine Humans Anaerobiosis Cell Proliferation chemotherapy mesenchymal stem cells human stromal dermal fibroblasts drug delivery business.industry Melanoma Mesenchymal stem cell Biological activity Cell cycle Fibroblasts medicine.disease Coculture Techniques 030104 developmental biology chemistry Apoptosis 030220 oncology & carcinogenesis Drug delivery Cancer research business |
| Zdroj: | Clinical and experimental dermatology. 41(4) |
| ISSN: | 1365-2230 |
| Popis: | SummaryBackground Drug toxicity currently represents the main challenge of tumour chemotherapy. Our group recently developed a new method for drug delivery inspired by the ‘Trojan Horse’ concept. Human mesenchymal stem cells (hMSCs) have been shown to play the role of new ‘horses’ in delivering anti-tumour agents, without involving any genetic manipulation. As human stromal dermal fibroblasts (hSDFs) represent an interesting alternative to hMSCs, being easy to isolate, they could be an ideal candidate for this kind of procedure. Aim To investigate whether hSDFs can take up and deliver paclitaxel (PTX) in sufficient concentrations to inhibit a very aggressive melanoma tumour (IgR39) in vitro. Methods hSDFs were primed with high doses of PTX, and then the effect of drug delivery on IgR39 melanoma proliferation in vitro was evaluated using several assays (antiproliferation, transwell cocultures, rosette assays and colony growth assays). Furthermore, the cell cycle and PTX uptake/release mechanism of hSDFs were studied both under both normal and hypoxic conditions. Results hSDFs incorporated PTX and then released it with unaffected pharmacological activity, inhibiting human IgR39 melanoma growth in vitro. The hypoxic conditions did not induce changes in cell cycle pattern and the uptake–release mechanism with PTX was not affected. Conclusions hSDFs can be used as a Trojan horse, as the released drug was functionally active. These results indicated that these cells could be used for clinical treatment as the drug was released into the cellular environment and the primed cells underwent apoptosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text