An Engineered Mesenchymal Stem Cell Expressing CD44 as a Candidate to Target Colon Cancer Tissue in Mice Model

It is evident that the success of common cancer treatments is reduced due to limited drug access to tumor tissue, the drug toxicity intolerance in healthy cells, as well as the exposure of the immune system to the drug. Cancer stem cells are also a small population of tumor cells, which have different potentials for regeneration, proliferation, and differentiation and serve as a carcinogenic driving force. They are believed to play a key role in the onset, progression, drug resistance, recurrence of cancer, or metastasis. Although mesenchymal stem cells (MSC) have a slight ability to migrate toward the tumor, they could be considered as a cellular carrier for tumor targeting due to lack of recognition by the host immune system. Stem cells with their own ligands could effectively target cancer cells. One of the CD markers that exist on the surface of stem cells is CD44v6, which is considered as a homing receptor. Given that the expression level of stem cell markers is reduced during consecutive cultures in vitro environment; therefore, in the present study, stem cells were engineered using CD44 lentiviral vectors to more effectively improve the implantation and targeting of the colon cancer cell model.

In this study, the structure of the CD44 gene was designed in lentiviral vectors and transfected to the HEK293T cell line along with auxiliary plasmids PSPAX2 and PMDG2. The growth medium of virus-containing cells was collected at optimized intervals, and transduction into mice mesenchymal stem cells, injection into mice, and homing processes were traced.

Successful production of lentiviral vectors and proper expression of the corresponding factor after transduction were effective in improving the MSC homing in cancer cell.

According to these findings, it could be suggested that high expression of CD44v6 factor could be effective in improving the implantation process in cancer cells and targeting treatment.