TABLE 1.
Recent studies on the potential therapeutic effect of fibroblast reprogramming on SCI.
| Subject | Induction method | Cell type | Achievements | References |
| Rat | Small molecules (CHIR99021, forskolin, LDN193189, SB431542, SP600125, VPA, and Y-27632) | Neurons | Fibroblasts were converted to neurons in vitro; a neural network on a 3D porous filament scaffold, i.e., a neural scaffold was formed; transplantation of this neural scaffold into rats with spinal cord transection promoted motor recovery and axonal regeneration. | Hu et al., 2019 |
| Human | Alternating administration of two combinations of small molecules to the medium (Combination I: CHIR99021, LDN193189, RG108, dorsomorphin, P7C3-A20, A83-01, and ISX9; combination II: forskolin, Y27632, DAPT, PD0325901, A83-01, PMA, and P7C3-A20) | Glutamatergic neuron-like cells | Fibroblasts were converted to glutamatergic neuron-like cells in vitro (Based on transcriptional profiles, electrophysiological function, and synaptic activity) |
Yang et al., 2019 |
| Mouse | Lentivirus-mediated transcription factors (Ascl1, Pou3f2, Myt1l) | Neurons (including glutamatergic neurons and GABAergic neurons) | Fibroblasts were converted to glutamatergic neurons and GABAergic neurons in vitro | Vierbuchen et al., 2010 |
| Human | Lentivirus-mediated transcription factors (Ascl1, Pou3f2, Myt1l, and Neurod1) | Neurons (Predominantly glutamatergic neurons) | Fibroblasts were converted to glutamatergic neurons in vitro | Pang et al., 2011 |
| Pig | Lentivirus-mediated miR-124 and miR-9/9* combined with Ascl1 | glutamatergic neurons and GABAergic neurons | Fibroblasts were converted to glutamatergic neurons and GABAergic neurons in vitro | Habekost et al., 2020 |
| Mouse and human | Mouse: Lentivirus-mediated transcription factors (Ascl1, Pou3f2, Myt1l, Lhx3, Hb9, Isl1, and Ngn2) Human: Lentivirus-mediated transcription factors (Ascl1, Pou3f2, Myt1l, Lhx3, Hb9, Isl1, Ngn2, and Neurod1) |
Motor neurons | Fibroblasts were converted to motor neurons (formed synapses and had action potentials) in vitro; The fibroblast-converted motor neurons integrated into the spinal cord after transplantation in vivo |
Son et al., 2011 |
| Mouse | Lentivirus-mediated transcription factors (Isl1 and Ngn2) | Motor neurons | Fibroblasts were converted to motor neurons (with spontaneous postsynaptic currents and repetitive action potentials) in vitro | Zhou et al., 2021 |
| Human | Lentivirus-mediated transcription factor Oct4 and further induction with Lhx3 | Motor neurons | Fibroblasts were converted to motor neurons (based on transcriptional profiles, electrophysiological function, synaptic activity, and the formation of neuromuscular junctions) in vitro; Motor function recovery was promoted after transplanting these fibroblast-converted motor neurons in rodent SCI models |
Lee et al., 2020 |
| Human | Lentivirus-mediated miR-124 and miR-9/9* combined with Isl1 and Lhx3 | Motor neurons | Fibroblasts were converted to motor neurons in vitro | Abernathy et al., 2017 |
| Human and mouse | Small molecules (kenpaullone, Forskolin, Y-27632, PMA, and RA) | Motor neurons | Fibroblasts were converted to motor neurons in vitro Motor neurons were detected in the dorsal skin of adult mice after transplantation of AG1-X2 beads (with five small molecules) in vivo |
Qin et al., 2018 |
| Human | Lentivirus-mediated transcription factors (Ngn2, Sox11, Isl1, and Lhx3), forskolin and dorsomorphin | Motor neurons | Fibroblasts were converted to motor neurons (on the basis of cytological and electrophysiological properties and the formation of functional neuromuscular junctions with skeletal muscle) in vitro | Liu et al., 2016 |
| Mouse | Lentivirus-mediated transcription factor combination I (Olig1, Olig2, Nkx2.2, Nkx6.2, Sox10, ST18, Gm98, and Myt1) Lentivirus-mediated transcription factor combination II (Nkx6.2, Sox10, and Olig2) |
Oligodendrocyte progenitor cells | Fibroblasts were converted to oligodendrocyte progenitor cells (on the basis of bipolar morphology and gene expression profiles) in vitro; Host axons were encapsulated, and dense myelin sheaths were produced in vivo in hypomyelinating mice after transplanting this fibroblast-converted oligodendrocyte progenitor cells |
Najm et al., 2013 |
| Mouse | Retrovirus-mediated transcription factor Oct4 | Oligodendrocyte progenitor cells | Fibroblasts were converted to oligodendrocyte progenitor cells in vitro; functional recovery was promoted, and the risk of tumor formation was reduced after transplanting in vivo in an SCI model | Kim et al., 2015 |
| Mouse | Retrovirus-mediated transcription factors (Pou3f4, Sox2, Klf4, c-Myc, and Tcf3) and the small molecule PDGF-AA | Oligodendrocyte progenitor cells | Fibroblasts were converted to oligodendrocyte progenitor cells in vitro; the recovery of motor function and expression of myelin basic protein was promoted after transplanting in vivo in an SCI model |
Lee et al., 2018 |