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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]