Isolation of human mesenchymal stem cells and their use in regenerative and gene therapy

We prepared humna mesenchymal stem cells expressing yeast fusion cytosine deaminase::uracil phosphoribosyltransferase gene(CDATMSC) by retrovirus transduction. We explored their therapeutic potential on a model of human colon cancer in the presence of prodrug 5 fluorocytosine. CD-AT-MSC in combination with 5-fluorocytosine augmented bystander effect and selective cytotoxicity on target tumor cells HT 29 in vitro. We confirmed directed migration ability of AT-MSC and CD-AT-MSC towards tumor HT 29 both in vitro and in vivo. We achieved significant inhibition of tumor growth by s.c. or i.v. administered CD-AT-MSC in nude mice. In conclusion these data characterize mesenchymal stem cells derived from adipose tissue as suitable delivery vehicles for prodrug converting gene and show their utility for a personalized cell based targeted cancer gene therapy.