Affordable Access

deepdyve-link
Publisher Website

3D multicellular models reflect the efficiency of MSC-directed enzyme/prodrug treatment.

Authors
  • Bohovic, R
  • Demkova, L
  • Cihova, M
  • Skolekova, S
  • Durinikova, E
  • Toro, L
  • Tyciakova, S
  • Kozovska, Z
  • Matuskova, M
  • Kucerova, L
Type
Published Article
Journal
Neoplasma
Publication Date
Jan 01, 2015
Volume
62
Issue
4
Pages
521–530
Identifiers
DOI: 10.4149/neo_2015_063
PMID: 25997965
Source
Medline
Keywords
License
Unknown

Abstract

Mesenchymal stromal cells (MSC) exhibit beneficial properties to serve as cellular vehicles for enzyme/prodrug cancer gene therapy approaches. We have previously shown that engineered human adipose tissue-derived MSC in combination with non-toxic prodrug mediated substantial cytotoxic and antitumor effect. The aim of this study was to develop advanced 3D cultivation method to serve for modelling of the therapeutic outcome in vitro. We have used engineered MSC expressing fusion transgene cytosine deaminase::uracilphosphoribosyltransferase (CD-MSC) in combination with prodrug 5-fluorocytosine (5FC). This therapeutic regimen designated CD-MSC/5FC was combined with the human melanoma cells A375 or EGFP-A375 in both standard monolayer culture and 3-dimensional (3D) multicellular nodules. The extent of cytotoxicity was evaluated by standard viability assay MTS, ATP-based luminescence assay, fluorimetric test, measurement of Caspase-3/7 activation and DNA laddering. The data have shown that the extent of cytotoxic bystander effect mediated by CD-MSC/5FC is significantly lower in 3D culture conditions. However, these data better recapitulate the therapeutic efficiency as observed previously in vivo. We suggest here to use the 3D multicellular culture conditions for better prediction of the therapeutic outcome in mouse xenograft models.

Report this publication

Statistics

Seen <100 times