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Table 2 Summary of the procedures for reprogramming and the targeted functions in human pluripotent stem cells and their derivatives

From: Prevention of tumor risk associated with the reprogramming of human pluripotent stem cells

Cell Types Method Function targeted Status of tumorigenesis Tumor treatment Clinical trail References
A. Chemical treatments
 hPSCs Inhibitors of stearoyl-CoA desaturase (SCD)1 Oleate = decreased Stearate and Palmitate = increased Prevent teratoma Teratoma (No trial yet) 2013 [325]
 ESCs and EBCs (N-oleoyl serinol) = ceramide analogue S18 OCT4 (+) / Prostate apoptosis response-4 (PAR-4) (+) = elimination Human cancer cell lines
Brain tumor cell lines
Adenocarcinoma cell lines
Hepatocarcinoma cell lines
2002 [336]
2003 [337]
 hESCs MitoBlock-6 Inhibit ERV/ALR (sulfhydroxyl oxidase) Impairs import of Mila40/Erv1 and TIM22
Block the teratoma formation
Teratoma 2013 [326]
 hPSCs, HiPSCs Clostridium perfringens endotoxin (CPE) Bound several Claudins including Claugin-6 Elimination of tumorigenic PSCs Teratoma 2013 [333]
 hESCs, hiPSC-derived cells Survivin inhibitor (Quercetin or YM155) Cell death of undifferentiated stem cells, mitochondrial accumulation of p53 Prevent teratoma formation Gastric cancer 2017 [338]
 hESCs Digoxin and Lanatoside C Cytotoxicity in undifferentiated hESCs Tumor prevention in hESCs Teratoma 2017 [339]
 hESCs JCO11 ER stress;
PERK/AT4/DDIT3
pathway
Inhibition of teratoma formation Teratoma 2014 [340]
B. Immunological treatment
 hPSCs Anti-Claudin 6 (CLDN-6), Anti-CLDN-6 (+) cells removal, Anti-CLODN-6-Cytotoxic Ab, Anti-CLODN-6-Toxin CPE Decrease the teratoma-formation Inhibition of Teratoma Teratoma 2013 [333]
 hPSCs Anti-SSEA-5 H-type-1 glycan surface markers, SSEA-5-CD9, CD30, CD50, CD90 and CD200 Removal of cells with teratoma-potential from incompletely differentiated hESCs Teratoma 2011 [323]
 hPSCs UEA-1+ and SSEA-4+ Fut1 and Fut 2 (fucosyl transferases) Enrichment of PSCs Teratoma 2011 [341]
 hESCs mAb 84 cytotoxic antibody(Podocalyxin-like protein 1) Kill undifferentiated hSCs Removal of teratoma formation Teratoma 2009 [331]
2008 [332]
 HPSCs derived neural precursor cells Tra-1-60 (−), Tra-1-81 (−) Removal of undifferentiated cells by Ab-nanogold Inhibition of teratoma formation Teratoma 2010 [342]
C. Genetic treatment
 hESCs Survivin (BIRC5), YM155 Apoptosis in hESCs and teratoma formation Removal of teratoma formation Teratoma 2009 [328]
 hESCs HSV-tk + cells were killed by ganciclovir Kill HSV-tk (+) cells Remove the tumor forming cells HSV-tk + teratoma 2003 [330]
 hESCs Nanog-3′ untranslated region with HSV-tk (+) gene Kill HSV^tk (+) cells Remove the tumor forming cells Teratoma 2012 [343]
 Gastric cancer cells Overexpression of JDP2, Oct4 BMP7 inhibition Decreasing teratoma development Gastric cancer 2017 [195]
 Neural cells from iPSCs Pre-evaluation by transfer of iPSCs derived cells to primates Pre-evaluation of tumor development No tumor development Spinal cord injury in marmoset model 2012 [344]
 Neural cells from iPSCs Methylation analysis of iPSCs derived cells Non-methylation status of CAT, PSMD5 genes No tumor development Nerval stem progenitors hiPSC-NS/DCs in clinical model 2017 [303]
 Prostate cancer cells Knock down of Oct4, Sox2 Tumor development screening after in vivo transfer No tumor development Prostate cancer
DU145.DC3
2010 [314]
 Cardiac progenitor cells from iPSCs Inhibitors of DNA topoisomerase Decreasing teratoma formation Decreasing teratomas Teratoma iPSC-derivet cardiac regenerations 2014 [345]
 ES cells CDK1 inhibitor treatment Activation of p53-HOXA-MCL1 axis Prevention of teratoma formation Teratoma 2015 [346]
 iPSCs Inhibition of anti-apoptotic factor, treatment Survivin (YM155) Pre-evaluation of tumor development No teratoma formation in mice Teratoma 2017 [347]
 iPSCs Introduction of suicide gene Caspase-9 Pre-evaluation of tumorigenic transformation Avoid tumorigenic transformation Injured spial cord of NOD/SCID mice hiPS/NS/DCs in animal model 2017 [348]
2012 [344]
 Neuro-spheres from iPSCs Pre-evaluation by transfer of iPSCs derived cells to mice Pre-evaluation of tumor development No tumor development Spinal cord injury (SCI) patients tratment in animal model hiPS/NS/DCs in animal model 2011 [349]
 Pancreatic ductal adenocarcinoma derived PDAC * Tet-OSKM & MzrtTA
* Mir302-OCT4 * Episomal vector
Reduced tumorgenicity
TET2, SirT1, and Dot1L were decreased. TET1 upregulated & Tbx downregulated
Nanog is required. Tra-1-80 decreased Reprogrammed pancreatic ductal adenocarcinoma (PDAC)-Tumergenesis 2019 [350]
 Ischemic Cardiomyopathy cells EZH2, FoxM1 epigenetic repressed in PRC2
KLF15 decreased
DNA methylation on targetsof KLF15 Epigenetic regulator suppressed metabolic reprogramming of ICM KLF15 repression Ischemic cardiomyopathy
(ICM)-Reprogramming
2019 [351]
 Ovarian cancer cells C/EBPBeta-DOT1L Open chromatin H3K79 methylation Ovarian cancer cells-Reprogramming 2018 [352]
 Pediatric cancer derived iPSCs Dnmt3a ablation De novo ICR-preferred CGI hypermethylation ICR-CpG islands Cancer repressed In vivo pluripotency 2017 [353]