TY - JOUR
T1 - Paclitaxel priming of trail expressing mesenchymal stromal cells (M-scs-trail) increases antitumor efficacy of their secretome
AU - Coccè, Valentina
AU - Bonomi, Arianna
AU - Cavicchini, Loredana
AU - Sisto, Francesca
AU - Giannì, Aldo
AU - Farronato, Giampietro
AU - Alessandri, Giulio
AU - Petrella, Francesco
AU - Sordi, Valeria
AU - Parati, Eugenio
AU - Bondiolotti, Gianpietro
AU - Paino, Francesca
AU - Pessina, Augusto
N1 - Funding Information:
The authors thanks Drs. Massimo Dominici and Giulia Grisendi for supplying the adipose-derived mesenchymal stromal cells expressing TRAIL (MSCs-TRAIL) and for the interesting discussion on this topic. We thanks Dr.ssa Ros-alind Hendricks (IRCCS Istituto Neurologico Besta) for the text revision for the English language.
Publisher Copyright:
© 2021 Bentham Science Publishers.
PY - 2021
Y1 - 2021
N2 - Background: Adipose tissue-derived MSCs engineered with the tumor necrosis fac-tor-related apoptosis-inducing ligand protein (MSCs-TRAIL) have significant anticancer activity. MSCs, without any genetic modifications, exposed to high doses of chemotherapeutic agents are able to uptake the drug and release it in an amount affecting tumor proliferation. The purpose of this study was to verify the ability of MSCs-TRAIL to uptake and release paclitaxel (PTX) by pro-viding an increased antitumor efficacy. Methods: MSCs and MSCs-TRAIL were tested for their sensitivity to Paclitaxel (PTX) by MTT as-say, and the cells were loaded with PTX according to a standardized procedure. The secretome was analysed by HPLC for the presence of PTX, microarray assay for soluble TRAIL (s-TRAIL) and tested for in vitro anticancer activity. Results: MSCs-TRAIL were resistant to PTX and able to incorporate and then release the drug. The secretion of s-TRAIL by PTX loaded MSCs-TRAIL was not inhibited, and the PTX delivery together with s-TRAIL secretion resulted in increased antitumor efficacy of cell secretome as tested in vitro on human pancreatic carcinoma (CFPAC-1) and glioblastoma (U87-MG). Conclusion: Our result is the first demonstration of the possible merging of two new MSCs therapy approaches based on genetic manipulation and drug delivery. If confirmed in vivo, this could po-tentiate the efficacy of MSCs-TRAIL and strongly contribute to reducing the toxicity due to the systemic treatment of PTX.
AB - Background: Adipose tissue-derived MSCs engineered with the tumor necrosis fac-tor-related apoptosis-inducing ligand protein (MSCs-TRAIL) have significant anticancer activity. MSCs, without any genetic modifications, exposed to high doses of chemotherapeutic agents are able to uptake the drug and release it in an amount affecting tumor proliferation. The purpose of this study was to verify the ability of MSCs-TRAIL to uptake and release paclitaxel (PTX) by pro-viding an increased antitumor efficacy. Methods: MSCs and MSCs-TRAIL were tested for their sensitivity to Paclitaxel (PTX) by MTT as-say, and the cells were loaded with PTX according to a standardized procedure. The secretome was analysed by HPLC for the presence of PTX, microarray assay for soluble TRAIL (s-TRAIL) and tested for in vitro anticancer activity. Results: MSCs-TRAIL were resistant to PTX and able to incorporate and then release the drug. The secretion of s-TRAIL by PTX loaded MSCs-TRAIL was not inhibited, and the PTX delivery together with s-TRAIL secretion resulted in increased antitumor efficacy of cell secretome as tested in vitro on human pancreatic carcinoma (CFPAC-1) and glioblastoma (U87-MG). Conclusion: Our result is the first demonstration of the possible merging of two new MSCs therapy approaches based on genetic manipulation and drug delivery. If confirmed in vivo, this could po-tentiate the efficacy of MSCs-TRAIL and strongly contribute to reducing the toxicity due to the systemic treatment of PTX.
KW - CFPac-1
KW - Drug delivery mechanism
KW - Paclitaxel
KW - Secretome
KW - TRAIL-Mesenchymal stromal cells
KW - U87-MG
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U2 - 10.2174/1568009620666201116112153
DO - 10.2174/1568009620666201116112153
M3 - Article
C2 - 33200709
AN - SCOPUS:85105505668
VL - 21
SP - 213
EP - 222
JO - Current Cancer Drug Targets
JF - Current Cancer Drug Targets
SN - 1568-0096
IS - 3
ER -