Table 1.
Neural differentiation approaches in 2D and 3D using stem cells.
| Type | Desired cell or tissue type | Approaches | Characteristics | Cell | References |
|---|---|---|---|---|---|
| 2D | Motor neuron differentiation | • RA, SHH treatment | • Differentiation into spinal progenitor cells and motor neurons • Transplantation of RA and SHH treated EBs into stage 15–17 chick spinal cord |
mESCs | Wichterle et al., 2002 |
| Midbrain DA neuron differentiation | • Stromal cell co-culture • Serum-free condition, LIF removal |
• Promoted neural differentiation by SDIA • Anti-neutralizing effect of BMP4 |
mESCs | Kawasaki et al., 2000 | |
| Midbrain DA neuron differentiation | • Stromal cell co-culture in serum replacement medium • For midbrain DA neuron : N2 medium supplemented with growth factors at various timepoints (SHH, FGF8, BDNF, GDNF, TGFb3, cAMP, and AA) |
• Promoted neuroectodermal differentiation by co culture with stromal cells • Efficient midbrain DA neuron derivation |
hESCs | Perrier et al., 2004 | |
| Neural precursor cell differentiation | • FGF2 treatment after EB formation | • Formation of neural tube-like structure • Differentiation potential into neurons, astrocytes, and oligodendrocytes • Incorporation of NPCs after transplantation into neonatal mouse brain |
hESCs | Zhang et al., 2001 | |
| Neural rosette structure formation Midbrain DA neuron and motor neuron differentiation |
• Noggin, SB431542 treatment (Dual-SMAD inhibition) • For midbrain DA neuron : Dual-SMAD inhibition (days 1–5), SHH (days 5–9), BDNF, ascorbic acid, SHH, and FGF8 (days 9–12), BDNF, ascorbic acid, GDNF, TGFb3, and cAMP (days 12–19) • For motor neuron : Dual-SMAD inhibition (days 1–5), BDNF, ascorbic acid, SHH, and RT (days 5–11) |
• Conversion of more than 80% of hESCs into neural lineage • Further differentiation into midbrain DA neuron and motor neuron |
hESCs | Chambers et al., 2009 | |
| Primitive NSCs (pNSCs) differentiation | • Gibco PSC Neural induction medium | • Efficient induction of pNSCs within 7 days • Expression of NSC marker Pax6, Sox1, Sox2, and Nestin • Differentiation potential to neurons, astrocytes, and oligodendrocytes |
hESCs | Yan et al., 2013 | |
| Primitive NSCs (pNSCs) differentiation | • FGF2 and hLIF treatment with GSK inhibitor (CHIR99021) and MEK inhibitor (PD0325901) | • Expression of NSC marker Pax6, Sox1 and N-CAD • Differentiation potential to neurons, astrocytes, and oligodendrocytes |
hiPSCs | Shin et al., 2019 | |
| 3D in vitro | NSC proliferation Neural and glial cells differentiation |
• 3D peptide scaffold using self-assembly proteins (SAPs) | • Survival and proliferation of NSCs in 3D peptide scaffold • Differentiation potential to neurons, astrocytes, and oligodendrocytes |
mNSCs | Cunha et al., 2011 |
| Transdifferentiation into neuronal or glial cell types |
• 3D scaffold synthesized with collagen and hyaluronic acid | • Changes in differentiation potency by scaffold stiffness • Neuronal differentiation in soft scaffold and glial differentiation in stiff scaffold |
hMSCs | Her et al., 2013 | |
| Neuronal differentiation | • 3D artificial nanofiber networks | • Rapid and selective differentiation into neurons in artifical nanofiber scaffold | mNPCs | Silva et al., 2004 | |
| 3D in vivo | NSC differentiation | • Teratoma formation | • In vivo isolation of NSCs from miPSCs with defected differentiation potency in vitro
• Expression of NSC marker Nestin, and Sox2 • No secondary tumor formation |
mESCs,miPSCs | Hong et al., 2016 |
| NSC differentiation | • Chimera formation | • Expression of NSC marker Nestin, and Sox2 • More similar gene expression pattern to brain-derived NSCs than in vitro-differentiated NSCs |
mESCs | Choi et al., 2017 |