{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T11:55:14Z","timestamp":1790942114028,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Previously, we validated capability of human adipose tissue\u2010derived mesenchymal stem cells (AT\u2010MSC) to serve as cellular vehicles for gene\u2010directed enzyme prodrug molecular chemotherapy. Yeast fusion cytosine deaminase : uracil phosphoribosyltransferase expressing AT\u2010MSC (CD<jats:sub>y<\/jats:sub>\u2010AT\u2010MSC) combined with systemic 5\u2010fluorocytosine (5FC) significantly inhibited growth of human colon cancer xenografts. We aimed to determine the cytotoxic efficiency to other tumour cells both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CD<jats:sub>y<\/jats:sub>\u2010AT\u2010MSC\/5FC\u2010mediated proliferation inhibition against a panel of human tumour cells lines was evaluated in direct and indirect cocultures <jats:italic>in vitro<\/jats:italic>. Antitumour effect was tested on immunodeficient mouse model <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Although culture expansion of CD<jats:sub>y<\/jats:sub>\u2010AT\u2010MSC sensitized these cells to 5FC mediated suicide effect, expanded CD<jats:sub>y<\/jats:sub>\u2010AT\u2010MSC\/5FC still exhibited strong bystander cytotoxic effect towards human melanoma, glioblastoma, colon, breast and bladder carcinoma <jats:italic>in vitro<\/jats:italic>. Most efficient inhibition (91%) was observed in melanoma A375 cell line when directly cocultured with 2% of therapeutic cells CDy\u2010AT\u2010MSC\/5FC. The therapeutic paradigm of the CDy\u2010AT\u2010MSC\/5FC system was further evaluated on melanoma A375 xenografts on nude mice <jats:italic>in vivo<\/jats:italic>. Complete regression in 89% of tumours was achieved when 20% CD<jats:sub>y<\/jats:sub>\u2010AT\u2010MSC\/5FC were co\u2010injected along with tumour cells. More importantly, systemic CD<jats:sub>y<\/jats:sub>\u2010AT\u2010MSC administration resulted in therapeutic cell homing into subcutaneous melanoma and mediated tumour growth inhibition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CD<jats:sub>y<\/jats:sub>\u2010AT\u2010MSC capability of targeting subcutaneous melanoma offers a possibility to selectively produce cytotoxic agent <jats:italic>in situ.<\/jats:italic> Our data further demonstrate beneficial biological properties of AT\u2010MSC as a cellular vehicle for enzyme\/prodrug therapy approach to molecular chemotherapy. 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