Inductor | Origin of MSCs | Steps | Time | Percentage of differentiation reported | Technique used to demonstrate differentiation | Functionality | Reference |
SB431542, dorsomorphine, TSA, RG-108, 8-BrcAMP, Rolipram and bFGF. | Human bone marrow adult | Induction with TSA 200 nM, RG-108 10 μM, 8BrcAMP 300 μM, Rolipram 1 μM and 20 ng bFGF, together with dorsomorphin 2 μM and SB431542 2 μM. | 3 weeks | 95% demonstrated by morphological changes of neuronal nature. 68.05% and 89.12% were demonstrated by positive immunofluorescence for HT and Nurr1, respectively.
| Neuronal morphology was observed under a microscope. Immunostaining for Sox2, NCAM, A2B5, NeuN, Map2, β-tubulin III, NSE, Nurr-1, ChAT, TH, NF, VGLUT1, SYP, SYN-1, GAB VGAT, GAD67, PITX3, and synaptophysin. Increased expression of Sox2, Map2, B3T, NSE, Nurr-1, ChAT, TH, NF, VGLUT1, SYP, SYN-1, VGAT, GAD67, and PITX3 by RT-PCR and by WB. | Synaptophysin immunostaining reveals synapse-like structures that form between differentiated cells. Presence of K+ current rectifier demonstrated by Patch-clamp. | [112]
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SB431542 and Dorsomorphine | Adipose tissue of adult humans | Induction with Dorsomorphin 2 μM and SB431542 20 μM | 14 days | 85% demonstrated by positive immunofluorescence for NSE. | Neuronal morphology was observed under a microscope. RT-PCR increased Pax6, Sox1, NF-200, NES, and β-tubulin III. Immunostaining for Pax6, Sox1, NF-200, NES, and β-tubulin III. Activation via Erk1/2, PI3K, and Akt by phosphorylation and inhibition phosphorylation SMAD 1/5/8 and 2 WB. | Neuronal differentiation in vivo when implanted subcutaneously in SCID CB-17 mice after treatment with DM and SB was demonstrated by expressing the specific GAP43 protein of the axon growth cone. | [113]
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bFGF, SB431542, noggin, LDN193289, ac. ascorbic, dbcAMP and BDNF. | Adipose tissue of adult humans | Pre-induction with 4 ng/ml bFGF, SB431542 10 μM, noggin 100 ng/ml and LDN193289 0.5 μM, for 8 days. Subsequent treatment with 200 μM of ascorbic acid for 14 days. Finally, exposure to 50 μM dbcAMP and 20 ng/ml BDNF | 12 days. | 93%, 37%, and 47% were demonstrated by positive immunofluorescence for Tuj1, GAD, and GABA, respectively.
| Neuronal morphology was observed under a microscope. Increased expression TuJ1, MAP2, Dlx5, Lhx6, GAD67, SCN1A, SCN5A, Nkx2.1, Dlx2, Dlx5y Lhx6, vGat1, vGlut2, GAD65, GAD67, CALB2, and GABRA1 by RT-PCR. Immunostaining for Tuj 1, Pax6, MAP2, NeuN, GFAP, OLIG2, NKX2.1, DLX2, LHX6, GAD, and GABA. | Ability to trigger action potentials, presence of voltage-activated ionic currents, and presence of an inhibitory postsynaptic current when exposed to NMDAR and AMPA antagonists. | [114]
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