Adipose-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.
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. [10.1158/0008-5472.CAN-09-1865]
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: | ||
Digital Object Identifier (DOI): | http://dx.doi.org/10.1158/0008-5472.CAN-09-1865 | |
Rivista: | ||
Volume: | 70 | |
Pagina iniziale: | 3718 | |
Pagina finale: | 3729 | |
Codice identificativo ISI: | WOS:000278486200031 | |
Codice identificativo Scopus: | 2-s2.0-77951749301 | |
Codice identificativo Pubmed: | 20388793 | |
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. [10.1158/0008-5472.CAN-09-1865] | |
Tipologia | Articolo su rivista |
File in questo prodotto:
File | Descrizione | Tipologia | |
---|---|---|---|
Grisendi G et al Can Research 2010.pdf | Post-print dell'autore (bozza post referaggio) | Administrator Richiedi una copia |
Pubblicazioni consigliate

I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris