Fig 1.
Illustration of the processes of Td, differentiation, and reprogramming. The respective details could be found in the text below. Td, transdifferentiation.
Table 1.
Examples of transdifferentiation of different cell types using various approaches
| Source cell | Target cell | TF or transdifferentiation factor used | Observation | References |
|---|---|---|---|---|
| Adipocyte-derived stem cells | Osteoblasts | Streptomycin, penicillin, amphotericin B, and amphotericin B with Cu2+ | Exposure of amphotericin B induced the osteogenesis of stem cells | Skubis et al. 2017 |
| Astrocyte | iN | Ascl1, Myt1l, Brn2a | Efficacy 0.4%–5.9% | Torper et al. 2013 |
| Astrocyte NG2 cell | iN | NeuroD1 |
| Guo et al. 2014 |
| Cardiac fibroblast | Cardiomyocytes | Gata4, Mef2c, Tbx5 |
| Qian et al. 2012 |
| Cardiac fibroblast | Cardiomyocytes | Gata4, Mef2c, Tbx5 |
| Inagawa et al. 2012 |
| Cardiac fibroblast | Cardiomyocytes | microRNAs 1, 133, 208, and 499 |
| Jayawardena et al. 2015 |
| Fibroblasts | Neurons | VPA | Neurons generated by histone deacetylase inhibitor mechanism Glutamatergic neurons generated | Hu et al. 2015a |
| Fibroblasts | Neurons | ISX9 | Inhibition of the BET family protein induces the transdifferentiation process | Li et al. 2015 |
| Fibroblasts | Cardiomyocytes | LIF | Transdifferentiation occurs through an intermediate state | Fu et al. 2015 |
| Fibroblasts | Hepatocytes | HGF | Human hepatic progenitors proliferate for at least 10 passages without losing differentiation potential in vitro | Kim et al. 2019 |
| Fibroblast | Corneal epithelial | TCF4, C/EBPδ, ∆Np63α and Corneal specific medium | Infection with TCF4, C/EBPδ, and ∆Np63α TFs and exposure of medium induce transdifferentiation | Cieślar-Pobuda et al. 2016 |
Fig 2.
Transdifferentiation of two different cells, astrocytes and fibroblasts cell, into neurons using two different methods. Astrocytes are transdifferentiated into neurons using different TFs (Ascl1, Myt1l, Brn2a, and Neuro D1), while fibroblasts transdifferentiated into neurons using small molecules (ISX9 and VPA). ASCL1: Achaete-scute homolog 1; ISX9, A neurogenesis-promoting small molecule; TFs, transcription factors; VPA, Valproic acid.
Table 2.
Features and pitfalls of different strategies of transdifferentiation
| Strategy | Advantages | Disadvantages | References |
|---|---|---|---|
| TFs |
|
| Zhang et al. 2023b |
| MicroRNA |
|
| Shen et al., 2023; Singh et al., 2020 |
| Small molecules or pharmacological agents |
|
| Jayawardena et al. 2012; Zhang et al. 2023b |
| Extracellular vehicles and 3D culture |
|
| Zhang et al. 2023b |
Fig 3.
Different intermediate states during the transdifferentiation. MX, UI, and PG denote the mix, unspecific, and progenitor intermediate states, respectively.
Fig 4.
Summary of different applications of transdifferentiation in tissue engineering, cellular therapy, disease modeling, and gene correction. Df, differentiation; iPSC, induced pluripotent stem cells; Td, transdifferentiation.
Table 3.
List of selected clinical trials involving iPSCs or iPSC reprogramming for treatment of various diseases
| NCT number | Title of study | Disease | Location of study |
|---|---|---|---|
| NCT04476225 | iPSCs for disease research | Hirschsprung disease | San Francisco, California, USA |
| NCT03883750 | iPSCs for Niemann–Pick disease | Niemann–Pick disease | Lahore, Pakistan |
| NCT02720939 | ASD-specific iPSCs for disease modeling | Autism spectrum disorder | Taipei, Taiwan |
| NCT02084407 | Induction of pluripotent stem cells from human fibroblasts of DM1 patients | Myotonic dystrophy | Paris, France |
| NCT05616338 | Modeling bronchial epithelium in severe asthma with human induced iPSC | Severe asthma | Montpellier, France |
| NCT01943383 | Pharmacogenomic evaluation of antihypertensive responses in iPSCs study | Hypertension | Gainesville, Florida, USA |
| NCT02193724 | Feasibility of generating pluripotent stem cells from patients with familial retinoblastoma | Retinoblastoma | Memphis, Tennessee, USA |
| NCT03872713 | Establishment of human cellular disease models for Morquio disease | Morquio disease | Lahore, Pakistan |
| NCT03867526 | Establishment of human cellular disease models for Wilson disease | Wilson disease | Lahore, Pakistan |
| NCT03696628 | Modeling and pharmacological targeting of genetic cardiomyopathy in children via cardiomyocytes derived from iPSCs | Cardiomyopathy, familial | Montpellier, Occitanie, France |
| NCT01808729 | CAUSE Trial: Patient specific-cellular characterization of fibromuscular dysplasia and high-risk atherosclerotic endothelium | Early onset CAD fibromuscular dysplasia | New York, New York, USA |
| NCT02162953 | Stem cell models of best disease and other retinal degenerative diseases | Adult onset vitelliform, macular dystrophy, autosomal dominant vitreoretinochoroidopathy, best vitelliform macular dystrophy, bestrophinopathy, retinal disease | Rochester, Minnesota, USA |
| NCT00953693 | Patient specific iPSCs | Eye disorders Hepatic disorders | Tehran, Iran, |
| NCT02464956 | Production of iPSC-derived (RPE) cells for transplantation in AMD | AMD | Location not provided |
| NCT03754088 | In vitro model of the cystic fibrosis bronchial epithelium via iPS technology | Cystic fibrosis |