EnglishAdipose-derived mesenchymal stromal/stem cells (AD-MSC) may offer efficient tools for cell-based gene therapy approaches. In this study, we evaluated whether AD-MSC could deliver proapoptotic molecules for cancer treatment. Human AD-MSCs were isolated and transduced with a retroviral vector encoding full-length human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a proapoptotic ligand that induces apoptosis in a variety of human cancers but not normal tissues. Although several studies have documented the antitumor activity of recombinant human TRAIL, its use in vivo is limited by a short half-life in plasma due to a rapid clearance by the kidney. We found that these limitations can be overcome using stably transduced AD-MSC, which could serve as a constant source of TRAIL production. AD-MSC armed with TRAIL targeted a variety of tumor cell lines in vitro, including human cervical carcinoma, pancreatic cancer, colon cancer, and, in combination with bortezomib, TRAIL-resistant breast cancer cells. Killing activity was associated with activation of caspase-8 as expected. When injected i.v. or s.c. into mice, AD-MSC armed with TRAIL localized into tumors and mediated apoptosis without significant apparent toxicities to normal tissues. Collectively, our results provide preclinical support for a model of TRAIL-based cancer therapy relying on the use of adipose-derived mesenchymal progenitors as cellular vectors.
| Data di pubblicazione: | 2010 |
| Titolo: | Adipose-derived mesenchymal stem cells as stable source of tumor necrosis factor-related apoptosis-inducing ligand delivery for cancer therapy |
| Autore/i: | Grisendi, Giulia; Bussolari, Rita; Cafarelli, Luigi; Petak, I.; Rasini, Valeria; Veronesi, Elena; DE SANTIS, Giorgio; Spano, Maria Carlotta; Tagliazzucchi, M.; Barti Juhasz, H.; Scarabelli, Laura; Bambi, F.; Frassoldati, A.; Rossi, G.; Casali, Christian; Morandi, Uliano; Horwitz, E. M.; Paolucci, Paolo; Conte, P.; Dominici, Massimo |
| Autore/i UNIMORE: | |
| Rivista: | |
| Volume: | 70 |
| Pagina iniziale: | 3718 |
| Pagina finale: | 3729 |
| Codice identificativo ISI: | WOS:000278486200031 |
| Codice identificativo Scopus: | 2-s2.0-77951749301 |
| Citazione: | Adipose-derived mesenchymal stem cells as stable source of tumor necrosis factor-related apoptosis-inducing ligand delivery for cancer therapy / Grisendi, Giulia; Bussolari, Rita; Cafarelli, Luigi; Petak, I.; Rasini, Valeria; Veronesi, Elena; DE SANTIS, Giorgio; Spano, Maria Carlotta; Tagliazzucchi, M.; Barti Juhasz, H.; Scarabelli, Laura; Bambi, F.; Frassoldati, A.; Rossi, G.; Casali, Christian; Morandi, Uliano; Horwitz, E. M.; Paolucci, Paolo; Conte, P.; Dominici, Massimo. - In: CANCER RESEARCH. - ISSN 0008-5472. - STAMPA. - 70(2010), pp. 3718-3729. |
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http://hdl.handle.net/11380/640282
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