TY - JOUR
T1 - Controlled secretion of the anticancer protein MDA-7 from engineered mesenchymal stem cells
AU - Sagara, Atsunobu
AU - Karasawa, Takeshi
AU - Igarashi, Katsuhide
AU - Otsuka, Maky
AU - Sugiura, Rei
AU - Kodama, Akihiro
AU - Yamashita, Mutsumi
AU - Narita, Minoru
AU - Kato, Yoshinori
PY - 2017
Y1 - 2017
N2 - Mesenchymal stem cells (MSCs) have been explored as a "live" carrier of cytokines for targeted cancer therapy, but, in earlier reports in the literature, the secretion process of therapeutic cytokines was not regulated. The purpose of this study was to generate MSCs to conditionally secrete the melanoma differentiationassociated gene-7 (MDA-7) tumor-suppressor protein. To control the secretion of MDA-7 from MSCs, a wellestablished tetracycline-controlled transcriptional activation system was incorporated into MDA-7 plasmid. MDA-7 gene expression was induced in the engineered MSCs only in the presence of doxycycline, as characterized by quantitative reverse transcription (qRT)-PCR. Enzyme-linked immunosorbent assay (ELISA) also revealed that the MDA-7 protein was secreted from the engineered MSCs only after the cells had been exposed to doxycycline. Both recombinant human MDA-7 protein and the conditioned medium from the engineered MSCs in the presence of doxycycline significantly inhibited tube formation of human umbilical vascular endothelial cells (HUVECs), indicating that our system could be used for targeted, antiangiogenic therapy. Overall, this study provides useful information on the potential use of engineered MSCs for the controlled secretion of therapeutic proteins, in this case MDA-7, for targeted cancer therapy.
AB - Mesenchymal stem cells (MSCs) have been explored as a "live" carrier of cytokines for targeted cancer therapy, but, in earlier reports in the literature, the secretion process of therapeutic cytokines was not regulated. The purpose of this study was to generate MSCs to conditionally secrete the melanoma differentiationassociated gene-7 (MDA-7) tumor-suppressor protein. To control the secretion of MDA-7 from MSCs, a wellestablished tetracycline-controlled transcriptional activation system was incorporated into MDA-7 plasmid. MDA-7 gene expression was induced in the engineered MSCs only in the presence of doxycycline, as characterized by quantitative reverse transcription (qRT)-PCR. Enzyme-linked immunosorbent assay (ELISA) also revealed that the MDA-7 protein was secreted from the engineered MSCs only after the cells had been exposed to doxycycline. Both recombinant human MDA-7 protein and the conditioned medium from the engineered MSCs in the presence of doxycycline significantly inhibited tube formation of human umbilical vascular endothelial cells (HUVECs), indicating that our system could be used for targeted, antiangiogenic therapy. Overall, this study provides useful information on the potential use of engineered MSCs for the controlled secretion of therapeutic proteins, in this case MDA-7, for targeted cancer therapy.
KW - Controlled secretion
KW - In vitro
KW - Melanoma differentiation-associated gene-7
KW - Mesenchymal stem cell
KW - Tet-On system
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M3 - Article
AN - SCOPUS:85007586486
SN - 0918-6158
VL - 40
SP - 113
EP - 117
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
IS - 1
ER -