Pluripotent Stem Cells Derived Mesenchymal Stromal Cells Improve Therapies for Advanced Cancers
International Conference on Stem Cell Engineering
2014
4th International Conference on Stem Cell Engineering
General Submissions
Poster Session
Monday, March 17, 2014 - 5:14pm to 5:16pm
Bone marrow Mesenchymal stromal cells (BM-MSCs) have a unique tumor-homing capacity and are a promising vehicle of gene therapy for advanced cancers. However, BM-MSCs are difficult to genetically engineer due to their limited expandability and may promote cancer progression. Large amount of MSC-like cells can be derived from embryonic stem cells (ESCs) or iPS cells, which will greatly facilitate engineering and expansion of MSCs carrying anti-cancer genes. Starting from a human iPS cell line CY2 free of reprogramming transgenes, we derived adherent cells expressing typical MSC surface markers (PSC-MSCs). These PSC-MSCs have the same karyotypes as the parental line and did not form teratoma in our initial studies, whereas the parent line did so robustly. Similar to BM-MSCs, these PSC-MSCs differentiated into bone and adipocytes in vitro, and showed homing property to cancer cells in vitro with comparable expression of genes related with tumor tropism. Notably, these PSC-MSCs express much low level of receptors for TGF-beta and Interleukin-1, two major cytokines inducing the pro-tumor activities of BM-MSCs. Consistently, after stimulation with TGF-beta, Interleukin-1 or tumor-conditioned medium, the expression of multiple pro-tumor factors was much lower in PSC-MSCs than that in BM-MSCs. Moreover, when co-cultured with various cancer cells, PSC-MSCs did not promote the epithelial-mesenchymal transition of cancer cells or expand the cancer stem cell population as BM-MSCs did. On the other hand, when stimulated with TNF-alpha and poly dA/dT, PSC-MSCs expressed high level of Trail and were capable to induce apoptosis of cancer cells in vitro. These data suggest that PSC-MSCs are a promising safer alternate of BM-MSCs with better expandability and genetic engineering potential.