TITLE:
Anticancer Gene-engineered MSC-mediated Cancer Cell Death: An Imaging Demonstration
AUTHORS:
Xu-Yong Sun, Zhuang Chen, Mani R. Moniri, Hong Lu, Long-Jun Dai, Garth L. Warnock
KEYWORDS:
Genetic Engineering; Mesenchymal Stem Cells; Gene Therapy; Cancer Therapy; PTEN
JOURNAL NAME:
Engineering,
Vol.4 No.10B,
January
17,
2013
ABSTRACT:
This study was performed to
demonstrate the transportation of an engineered MSC-produced
intracellular anticancer gene product between mesenchymal stem cell (MSC) and cancer cells. MSC-mediated
anticancer strategy has held great promise owing to MSCs’ capacity of
tumor-directed migration and the availability of specific anticancer
genes. All anticancer genes that have
been used in previous MSC-mediated
anticancer studies were limited in functioning via extracellular mechanisms,
mainly because of the restriction by cell membrane to macromolecules including
proteins. In order to apply the majority
of potent anticancer genes to the MSC-mediated
anticancer system, a specifically designed expression vector which bears an
intracellular anticancer gene, PTEN,
is utilized to demonstrate the feasibility of the system in cancer
therapies. A transacting activator of
transcription (TAT) was introduced into an expression vector followed by a
segment for PTEN-RFP fusion
protein. A direct demonstration of PTEN-RFP transportation between MSC and cancer cells was obtained from direct
co-cultures. A marked cancer cell death
was observed in indirect co-cultures with conditioned media from PTEN-transfected MSCs. The demonstration of PTEN-engineered
MSC-produced PTEN transportation indicates the feasibility of
applying intracellular anticancer gene expression system in MSC-mediated strategies for cancer therapy.