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