STB-HO, a novel mica fine particle, inhibits the teratoma-forming ability of human embryonic stem cells after in vivo transplantation

Pluripotent Stem Cells 0301 basic medicine Mice, Inbred BALB C Reverse Transcriptase Polymerase Chain Reaction Blotting, Western Human Embryonic Stem Cells Teratoma Mice, Nude Real-Time Polymerase Chain Reaction Mice 03 medical and health sciences Cell Transformation, Neoplastic Animals Humans Nanoparticles Aluminum Silicates Female RNA, Messenger Cells, Cultured Research Paper Stem Cell Transplantation
DOI: 10.18632/oncotarget.6472 Publication Date: 2015-12-05T04:52:46Z
ABSTRACT
Although pluripotent stem cell (PSC) therapy has advantages for clinical applications because of the self-renewal and multi-lineage differentiation abilities of PSCs, it also has disadvantages in terms of the potential for PSCs to undergo malignant transformation or unexpected differentiation. The prevention of teratoma formation is the largest hurdle of all. Despite intensive studies that have investigated ways to block teratomas, such methods have yet to be further developed for clinical use. Here, a new approach has focused on exerting anti-tumorigenic effects using a novel mica fine particle (MFP) designated STB-HO. Treatment with STB-HO regulated pluripotency- and apoptosis-related genes in differentiating human embryonic stem (hES) cells, while there is no effects in undifferentiated hES cells. In particular, STB-HO blocked the anti-apoptotic gene BIRC5 and activated p53, p21 and the pro-apoptotic proteins Bim, Puma and p-Bad during early spontaneous differentiation. Moreover, STB-HO-pretreated differentiating hES cells did not give rise to teratomas following in vivo stem cell transplantation. Our in vitro and in vivo results suggest a method for teratoma prevention in the context of PSC-derived cell transplantation. This novel MFP could break through the limitations of PSC therapy.
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