TABLE 2.
The methods used in recent years to reprogram cells from different sources into iSCs are summarized.
| Original cell | Induction factors | Phenotypic Markers | Animal model | Result | References |
| BMSCs | BME, RA, FSK, rbFGF, PDGF and HRG | p75,S-100,GFAP and O4 | Sciatic nerve injury | The GFP expressing MSCs differentiated into myelin cells and supported the regrowth of nerve fibers within 3 weeks after surgery. | Dezawa et al., 2001 |
| BMSCs | BME, RA, FSK, bFGF, PDGF and HRG | P0 and MAG | Sciatic nerve injury | ISCs-derived artificial grafts have a strong potential to promote peripheral nerve regeneration and can be used to reconstruct long distance gaps in difficult peripheral nerves. | Mimura et al., 2004 |
| BMSCs | BME, RA, FSK, bFGF, PDGF and HRG | PMP22,P0 and MBP | Facial nerve injury | Compared with BMSCs, iSCs provide a faster rate of axon extension and better quality of myelination for peripheral nerve regeneration. | Wang et al., 2011 |
| BMSCs | BME, RA, FSK, bFGF, PDGF and HRG, PROG, insulin and GLUCs. | GFAP, S100B, P0, and PMP22 | Sciatic nerve injury | The combined application of PROG, GLUC and insulin significantly improved the differentiation and culture conditions of classical iSCs, and enhanced the stability of morphology, phenotype and functional characteristics of iSCs in vitro, as well as the ability of axon growth and endogenous myelin sheath formation in vivo. | Liu et al., 2016 |
| ADSCs | engineered substrates with imprinted cell-like topographies | S100b, p75NTR, and Sox10 | – | Specific cell-like topography and associated micromechanical cues can directly differentiate ADSCs into Schwann cells. | Moosazadeh Moghaddam et al., 2019 |
| ADSCs | BME, RA, FSK, bFGF, PDGF and HRG | GFAP, S100 and p75 | – | Adipose stem cells can transdifferentiate into iSCs, which may be beneficial for the treatment of peripheral nerve injury. | Kingham et al., 2007 |
| ADSCs | BME, RA, FSK, bFGF, PDGF and HRG | GFAP, S100 and p75 | Common peroneal nerve injury | DASCs can be used as a substitute for autologous SCs to form myelin sheaths wrapped with axons in vivo, providing nutritional support for axons and promoting peripheral nerve regeneration. | Tomita et al., 2012 |
| ADSCs | BME, RA, FSK, bFGF, PDGF and HRG | S-100, p75 and integrin β4 | Sciatic nerve injury | DASCs can accelerate nerve conduction velocity, increase nerve fiber density and myelinated/unmyelinated fiber ratio, and rebuild nerves. | Orbay et al., 2012 |
| ADSCs | BME, RA, FSK, bFGF, PDGF and HRG, PROG, insulin and GLUCs. | S100B, GFAP, PMP22 and P0 | Sciatic nerve injury | The combined application of PROG, GLUC and insulin significantly improved the differentiation and culture conditions of classical iSCs, and enhanced the stability of morphology, phenotype and functional characteristics of iSCs in vitro, as well as the ability of nerve regeneration and functional recovery in vivo. | Kang et al., 2019 |
| MSCs | electrical stimulation by graphene electrodes | p75,α-S100 and α-S100β | – | MSCs can be transdifferentiated into Schwann cell-like phenotypes by electrical stimulation alone without additional chemical growth factors. | Das et al., 2017 |
| UCB-MSCs | BME, RA, FSK, bFGF, PDGF and HRG | GFAP and S-100 | – | In vitro, UCB-MSCs can differentiate into cells that resemble Schwann cells in morphology, phenotype, and function. | Zhang et al., 2009 |
| hESCs | N2, glutamine, penicillin, streptomycin, bFGF, FSK, NRG1 | GFAP, S100, HNK1, P75, MBP and PMP-22 | – | HESCs derived neurosphere cells can efficiently differentiate into iSCs with expression of SCs markers. | Ziegler et al., 2011 |
| Human pluripotent stem cells (hPSCs) | N2, B27, BSA, GlutaMAX, BME, CT 99021, SB431542, NRG1, forskolin, RA, PDGF-BB | S100B, NGFR, EGR2, and MPZ | Sciatic nerve injury | Two small molecules SB431542 (a TGF-β inhibitor) and CT99021 (GSK-3 inhibitor) and NRG1 were used and high-quality multipotent SCPs were produced. SCPs can be effectively differentiated into mature SCs with the functions of secreting GDNF, NGF, BDNF and NT-3, which can promote myelination of rat DRG axons in vitro and promote axonal regeneration of sciatic nerve injured mice in vivo. | Kim et al., 2017 |
| Skin fibroblasts | Lentiviral vectors | Erbb2, Erbb3, Cnx32, Pmp22 and Mpz | – | By driving the expression of two transcription factors, Sox10 and Egr2, human fibroblasts can be successfully transformed into iSCs with unique molecules and functions. | Mazzara et al., 2017 |
| SKIN fibroblasts | Retroviral vectors | S100B | Sciatic nerve injury | Transduction of SOX10 and Krox20 genes directly converts human fibroblasts into functional iSCs. ISCs can form myelin sheath and help mice recover from peripheral nerve injury. | Sowa et al., 2017 |
BMSCs, bone marrow mesenchymal cells; BME, beta-mercaptoethanol; RA, retinoic acid; FSK, forskolin; bFGF, basic-fibroblast growth factor PDGF, platelet derived growth factor; HRG, heregulin-beta1; GFP, green fluorescent protein; iSCs, induced Schwann-like cells; PROG, progesterone; GLUCs, glucocorticoids; ADSCs, adipose-derived stem cells; UCB-MSCs, umbilical cord blood-derived mesenchymal stromal cells; hESCs, human embryonic stem cells; NRG1, neuregulin-1; SCs, Schwann cells; MSCs, mesenchymal stem cells; hPSCs, human pluripotent stem cells; GSK-3, glycogen synthase kinase-3; GDNF, glial cell line-derived neurotrophic factor; NGF, nerve growth factor; BDNF, brain-derived neurotrophic factor; NT-3, neurotrophin-3; SCPs, Schwann cell precursors; DRG, dorsal root ganglion.