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.
Highlights
Stem cell therapy has emerged as a therapeutic strategy with great potential in the last few years
We found that STBHO treatment regulated pro- and anti-apoptotic factors, in early differentiating human embryonic stem (hES) cells; the effects of STB-HO were limited in embryoid bodies (EBs)
We hypothesized that STB-HO could influence the teratoma formation of hES cells by stimulating apoptosis
Summary
Stem cell therapy has emerged as a therapeutic strategy with great potential in the last few years. Human pluripotent stem cell (PSC), selfrenew indefinitely and can differentiate into all cell types of the human body With this excellent potential, they can be induced to differentiate into tissue-specific functional cells under proper cell culture conditions. They can be induced to differentiate into tissue-specific functional cells under proper cell culture conditions Such cell-specific differentiation protocols have improved and have been developed to obtain therapeutically relevant cell types from human PSC sources [4]. Despite excellent cell sources for the replacement of degenerative tissues, the clinical application of PSC therapies is strongly limited due to the potential for PSCs to form teratomas [10, 11]. Unless this risk is eliminated before transplantation, the teratoma issue is a central safety hurdle for the application of PSC therapies in regenerative medicine
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