Neural differentiation from pluripotent stem cells: The role of natural and synthetic extracellular matrix

Table 3 Protocols and in vivo studies for neural progenitor cells differentiation from human pluripotent stem cells

Growth factors	Cell source	Cell characteristics	Ref.
EB-based protocol
FGF-2/RA/ascorbic acid, db-cAMP, HAg	16 hiPSC lines	13 of the cell lines produced functional motor neurons. Treat with BDNF, GDNF, CNTF to produce motor neurons (4%-15% ISL+ neurons)	Boulting et al[43], 2011
RA/FGF-2	hESC lines: H7, hCSC14, hCSC14-CL1	Produce neuronal progenitors (> 95% nestin and Musashi-1), can become cholinergic neurons, GABA neurons, etc	Nistor et al[47], 2011
Isolated Rosette expanded with EGF/FGF-2	hiPSC lines	Generate long-term expandable neuro-epithelial like stem cells (Lt-NES); in stoke model, the cells improved recovery of fine forelimb movements	Oki et al[53], 2012
RA/Shh	hESC lines H1 and H9	To generate motor neurons (50% HB9+ motor neurons)	Hu et al[51], 2009
Monolayer-based protocol
Noggin and SB431542	hESC line: H9 hiPSC lines: iPS-14, iPS-27	> 80% PAX6+ cells; Shh/FGF8 for midbrain dopamine neurons; BDNF, Shh, RA, ascorbic acid for motor neurons	Chambers et al[12], 2009
Noggin and SB431542	hESC line: H9 hiPSC line: 253G4	Treat BDNF, GDNF, NT-3 for forebrain neurons which secrete Aβ for drug screening.	Yahata et al[52], 2011
Noggin only; FGF-2 may be added at later stage	hESC line: H1, H7, H9	> 90% nestin, musashi, and PSA-NCAM; For TH neurons, add Shh/FGF8/ascorbic acid; followed by BDNF, GDNF, ascorbic acid and laminin	Gerrard et al[48], 2005
FGF-2	hESC line: SA002 and AS034	> 90% nestin, NCAM; For neuronal lineage, add Shh/FGF8; after differentiation TH+ cells, MAPab+ cells and astrocytes existed	Axell et al[49], 2009

EB: Embryoid body; FGF-2: Fibroblast growth factor-2; RA: Retinoic acid; db-cAMP: Dibutyryl-cAMP; HAg: A small molecule agonist of the sonic hedgehog pathway; hESC: Human embryonic stem cell; hiPSC: Human induced pluripotent stem cell; BDNF: Brain-derived neurotrophic factor; GDNF: Glial cell-derived neurotrophic factor; CNTF: Ciliary neurotrophic factor; GABA: Gamma-Aminobutyric acid; Shh: Sonic hedgehog; NT-3: Neurotrophin-3; PSA-NCAM: Polysialylated-neural cell adhesion molecule; TH: Tyrosine hydroxylase; NCAM: Neural cell adhesion molecule.