Table 2.
Examples of the direct reprogramming with various methods
| Source cells | Target cells | Transgenes and/or Treatment | Species | Cell transplantation | Published year | PMID |
|---|---|---|---|---|---|---|
| Integration-free transduction | ||||||
| Fibroblasts (BJ and MRC-5 cells) | Hepatocytes | HNF1A and Any two of the three factors: FOXA1, FOXA3, and HNF4A (mRNA transfection) | Human | 2014 | 2496371559) | |
| Non-sensory cochlear epithelial cells | Neuronal cells | Ascl1; Ascl1 and Neurod (plasmid electroporation) | Mouse | 2014 | 2492835139) | |
| Cardiac fibroblasts | Cardiomyocytes | Gata4, Mef2c, and Tbx5 (peptide-enhanced mRNA transfection) | Mouse | 2015 | 25834424116) | |
| Astrocytes | Neural stem cells | Sox2 (Leu3p-αIPM system) | Mouse | 2016 | 27148066121) | |
| Fetal and embryonic fibroblasts and Brain cells in vivo | Neuronal cells | Ascl1, Brn2, and Myt1l (mRNA transfection with a GO-PEI-based reagent in vitro and in vivo) | Mouse & Human | 2016 | 2814563140) | |
| Peripheral blood mononuclear cells | Photoreceptor cells | CRX, RAX1, and NEUROD1 (SeV infection) | Human | 2016 | 27170256112) | |
| Gingival fibroblasts and Adult dermal fibroblasts | Osteoblasts | OCT4, OSTERIX, and L-MYC (plasmid transfection) | Human | YES | 2016 | 2699086081) |
| Fibroblasts | Hepatocytes | OCT4, FOXA2, HNF1A, and GATA3 (protein transduction with HVJ-E) | Human | 2017 | 2858733162) | |
| Fibroblasts | Neurocytes | SOX2, GATA3, and NEUROD1 (protein transduction with HVJ-E) | Human | 2017 | 2858733162) | |
| Fibroblasts (3T6 cells) | Neuronal cells | Ascl1, Brn2, and Foxa1 (plasmid transfection with a polysaccharide-based reagent) | Mouse | 2017 | 28855426119) | |
| Mesenchymal stem cells | Hepatocytes | Hnf4a and Foxa3 (PiggyBac transposon) | Mouse | 2017 | 28295042114) | |
| Dermal fibroblasts | Endothelial progenitor cells | ETV2 (mRNA transfection) | Human | YES | 2017 | 27778229117) |
| Fibroblasts (3T6 cells) | Neuronal cells | Ascl1, Brn4, and Tcf3 (plasmid transfection with a polysaccharide-based reagent) | Mouse | 2017 | 29137640120) | |
| Mesenchymal stem cells and Dermal fibroblasts | Neural stem cells | SOX2 (mRNA transfection) | Human | 2018 | 29909688118) | |
| Adult fibroblasts | Neural precursor cells | SOX2; SOX2 and PAX6; SOX2 and LMX1A; SOX2, LMX1A, and FOXA2 (plasmid transfection) | Human | 2018 | 3001847136) | |
| Dermal fibroblasts | Neural precursor cells | SOX2 and PAX6 (chemically modified mRNA or plasmid transfection) | Human | 2018 | 3045044034) | |
| Embryonic fibroblasts | Hepatocytes | Hnf4a and Foxa3 (modified mRNA transfection) | Mouse | YES | 2018 | 30327781115) |
| Foreskin fibroblasts | Neuronal cells | ASCL1 + miR-124 + P53 knockdown (episomal plasmid transfection) | Human | 2019 | 30539819122) | |
| Bone marrow-derived cells, Fibroblasts, and Keratinocytes | Neural precursor cells | MSI1, NGN2, and MBD2 (plasmid transfection) | Human | YES | 2019 | 3119617337) |
| Renal proximal tubular epithelial (HK2) cells | Nephron progenitor cells | SNAI2, EYA1, and SIX1 (PiggyBac transposon) | Human | 2019 | 30827514103) | |
| Chemical compounds (with or without transcription factors) | ||||||
| Fibroblasts (IMR90 or MRC5 cells) | Cholinergic neurons | NGN2 + Forskolin and dorsomorphin treatment | Human | 2013 | 23873306130) | |
| Embryonic fibroblasts and Neonatal tail-tip fibroblasts | Cardiomyocytes | CHIR99021, RepSox, Forskolin, Valproic acid, Parnate, and TTNPB treatment | Mouse | 2015 | 26292833123) | |
| Embryonic fibroblasts and Adult tail-tip fibroblasts | Neural stem cells | Valproic acid, Bix01294, RG108, PD0325901, CHIR99021, Vitamin C, and A83-01 treatment | Mouse | YES | 2015 | 26788068124) |
| Fibroblasts | Neuronal cells | Valproic acid, CHIR99021, RepSox, Forskolin, SP600125, GO6983, and Y-27632 treatment | Human | 2015 | 26253202125) | |
| Fibroblasts | Neuronal cells | ISX9, SB431542, Forskolin, CHIR99021, and I-BET151 treatment | Mouse | 2015 | 26253201126) | |
| Embryonic fibroblasts | Neural stem cells | A83-01, Purmorphamine, Valproic acid, and Thiazovivin treatment | Mouse | 2017 | 27207831131) | |
| Urine-derived cells | Hepatocytes | FOXA3 and HNF1A or HNF4A + CHIR99021, RepSox, Valproic acid, Parnate, TTNPB, and Dznep treatment | Human | 2018 | 30315254127) | |
| Embryonic and adult fibroblasts | Skeletal muscle progenitor cells | Myod + CHIR99021, RepSox, and Forskolin treatment | Mouse | YES | 2018 | 29742392128) |
| Adult dermal fibroblasts, Fetal pancreas fibroblasts, and Peripheral blood mononuclear cells | Neural plate border stem cells | BRN2, KLF4, SOX2, and ZIC3 + CHIR99021, ALK5 inhibitor, Purmorphamine, Tranylcypromine treatment | Human | YES | 2018 | 30581079132) |
| Striatal neurons | Dopaminergic neurons | Sox2, Nurr1, Lmx1a, and Foxa2 + Valproic acid treatment (in vivo infection) | Mouse | 2018 | 3031829242) | |
| Glioblastoma cells (U87MG cells) | Neuronal cells | Forskolin, ISX9, CHIR99021, I-BET151, and DAPT treatment | Human | 2018 | 30091580129) | |
| Dermal fibroblasts | Neuronal cells | NGN2 and ASCL1 + Pyrintegrin, ZM336372, AZ960, and KC7F2 treatment | Human | 2019 | 31099332133) | |
| Culture condition and soluble factors (with transcription factors) | ||||||
| Liver cells in vivo | β cells | PDX1 + EGF and nicotinamide treatment | Human | YES | 2005 | 15899968134) |
| Adult dermal fibroblasts and Neonatal foreskin fibroblasts | Multilineage blood progenitor cells | OCT4 + hematopoietic cytokines treatment | Human | YES | 2010 | 21057492135) |
| Embryonic fibroblasts | Cardiomyocytes | OSKM + cytokines (including Bmp4) treatment | Mouse | 2011 | 21278734136) | |
| Adult skin fibroblasts | Neural stem cells | OSKM + neurosphere culture | Mouse | YES | 2012 | 22467474137) |
| Amniocytes | Vascular endothelial cells | ETV2, FLI1, and ERG1 + TGFβ inhibitor treatment | Human | YES | 2012 | 23084400139) |
| Embryonic stem cells-derived fibroblasts | Neural crest cells | SOX10 + Environmental cues including WNT activation | Human | YES | 2014 | 25158936140) |
| Newborn fibroblasts | Hepatocytes | OSK + Soluble factors | Human | YES | 2014 | 24572354226) |
| Dermal fibroblasts | Oligodendrocyte progenitor cells | Oct4 + OPC induction medium | Mouse | YES | 2015 | 26497893141) |
| Embryonic fibroblasts | Keratinocytes | OSK + Bmp4 and RA treatment | Mouse | YES | 2016 | 27473056142) |
| Skin fibroblasts | Neural stem cells | OCT3/4, SOX2, KLF4, L-MYC, and LIN28 + P53 knockdown + Neurotrophins treatment | Human | 2016 | 27822179138) | |
| miRNAs (with or without transcription factors) | ||||||
| Cardiac fibroblasts | Cardiomyocytes | miR-1, miR-133, miR-208, and miR-499 | Mouse | 2012 | 22539765147) | |
| Embryonic fibroblasts | Neuronal cells | Ptb knockdown | Mouse | 2013 | 23313552143) | |
| Cardiac fibroblasts and Embryonic fibroblasts | Cardiomyocytes | Gata4, Mef2c, and Tbx5 + miR-133; Gata4, Mef2c, Tbx5, Mesp1, and Myocd + miR-133 | Mouse & Human | 2014 | 24920580148) | |
| Adult dermal fibroblasts, Umbilical cord blood cells, and Senescent somatic cells | Neural stem cells | SOX2 + HMGA2 expression or LET-7B inhibition | Human | YES | 2015 | 25600877144) |
| Fibroblasts | Cardiomyocytes | GATA4, MEF2C, TBX5, ESRRG, MESP1, MYOCARDIN, ZFPM2, and HAND2 + miR-1 | Human | 2017 | 28796841149) | |
| Adult fibroblasts | Neuronal cells | miR-9/9* and miR-124 | Human | 2017 | 28886366145) | |
| Adult fibroblasts | Spinal cord motor neurons | ISL1 and LHX3 + miR-9/9* and miR-124 | Human | 2017 | 28886366145) | |
| Brain vascular pericytes | Cholinergic neuronal cells | ASCL1, MYT1L, BRN2, and TLX3 + miR-124 | Human | YES | 2018 | 29453933146) |
| Physical stimulation (with or without transcription factors) | ||||||
| Embryonic fibroblasts | Neuronal cells | Ascl1, Brn2, and Myt1l + Substrate topography | Mouse | 2014 | 24709523153) | |
| Fibroblasts | Cardiomyocytes | Myocardin, Tbx5, and Mef2c + Microgroove | Mouse | 2015 | 26302234154) | |
| Embryonic fibroblasts | Dopaminergic neurons | Ascl1, Pitx3, Nurr1, and Lmx1a + Nanogroove | Mouse | 2015 | 25662493155) | |
| Dermal fibroblasts | Endothelial progenitor cells | ETV2 + Hypoxia | Human | 2016 | 27488544151) | |
| Neonatal tail-tip fibroblasts | Cardiomyocytes | Gata4, Mef2c, and Tbx5 + Microgroove | Mouse | 2016 | 27376554156) | |
| Fibroblasts | Cardiomyocytes | Gata4, Mef2c, and Tbx5 + Hypoxia | Mouse | 2016 | 26757100152) | |
| Dermal fibroblasts | Chondrocytes | Electrical stimulation | Human | 2019 | 31005261157) | |
| CRISPR/Cas9-based methods | ||||||
| Embryonic fibroblasts | Neuronal cells | CRISPR/Cas9-based transcriptional activators + gRNAs for Brn2, Ascl1, and Myt1l | Mouse | 2016 | 27524438158) | |
| Liver cells in vivo | β cells | CRISPR/Cas9-based transcriptional activators + gRNA for Pdx1 (in vivo infection) | Mouse | YES | 2017 | 2922478371) |
| Protein engineering (with transcription factors) | ||||||
| Embryonic fibroblasts | Cardiomyocytes | Gata4, Tbx5, and Hand2 + Mef2c fused with M3 domain of Myod | Mouse | 2013 | 23794713159) | |
| Astrocytes | Neuronal cells | Ascl1, Creb-VP16, and Icer | Mouse | 2017 | 28321434160) | |
| Other methods | ||||||
| Bone marrow stromal cells | Renal proximal tubular epithelial cells | HK2 cell-extracts treatment + streptolysin O | Human | YES | 2015 | 25754206161) |
| Embryonic fibroblasts | Cardiomyocytes | Gata4, Hand2, Mef2c, and Tbx5 + miR-1 and miR-133 + TGFβ inhibitors or ROCK inhibitors | Mouse | 2015 | 26354680162) | |
| Pancreatic exocrine cells | β cells | Pdx1, Ngn3, and Mafa (synthetic mRNA transfection) + 5-Aza treatment | Mouse | 2016 | 27187823163) | |
| Neonatal cardiac and tail-tip fibroblasts | Cardiomyocytes | miR-1, miR-133, miR-208, and miR-499 + three-dimensional culture | Mouse | 2016 | 27941896164) | |
| Neonatal cardiac and tail-tip fibroblasts | Cardiomyocytes | miR-1, miR-133, miR-208, and miR-499 + Reprogramming medium | Mouse | 2016 | 26975336165) | |
| Adipose-derived stem cells and Neonatal foreskin fibroblasts | Neural stem cells | iPSC induction followed by TRA-1-60–/SSEA4–selection | Human | YES | 2016 | 27569063166) |
| Fibroblasts | Adipocytes | OCT4 and C/EBPB (protein transduction with HVJ-E) + Adipogenic differentiation medium | Human | 2017 | 2858733162) | |