title: Human skin-derived fibroblasts used as a 'Trojan horse' for drug delivery.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Coccè
authors.affiliation: Department of Biosciences, Molecular Oncology Laboratory, University of Milan, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Vitale
authors.affiliation: Department of Biosciences, Molecular Oncology Laboratory, University of Milan, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Colombo
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bonomi
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Sisto
authors.affiliation: Department of Diagnostics and Applied Technology, Fondazione IRCCS Neurological Institute Carlo Besta, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ciusani
authors.affiliation: Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute Carlo Besta, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Alessandri
authors.affiliation: Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute Carlo Besta, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Parati
authors.affiliation: Department of Diagnostic Services, Desio and Vimercate's Hospital, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Brambilla
authors.affiliation: Department of Diagnostic Services, Desio and Vimercate's Hospital, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Brambilla
authors.affiliation: Department of Biosciences, Molecular Oncology Laboratory, University of Milan, Milan, Italy.
authors.forename: C A
authors.initials: CA
authors.lastname: La Porta
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pessina
mesh_terms: D000693:Anaerobiosis / Q000502:physiology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques / Q000379:methods*; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D017239:Paclitaxel / Q000008:administration & dosage*
chemical_list: D017239:Paclitaxel