Table 2.

Comparison of a representative selection of midbrain dopaminergic neuron differentiation protocols

Differentiation protocol	Brennand et al. [6]	Chambers et al. [80]	Fathi et al. [85]	Hartfield et al. [73]	Kriks et al. [81]	Perrier et al. [86]	Petit et al. [83]	Reinhardt et al. [84]	Tan et al. [87]
Duration (days)	110	19	30	66	50	62	90	28	28
Efficiency (TH+ cells)	8 %	ND (80 % PAX6+)	35 %	20.31 %	78 %	40 %	ND (75 % β-III-tubulin+)	35 %	33 %
Growth factors	AA, BDNF, dcAMP, FGF2, GDNF	AA, BDNF, cAMP, FGF2, FGF8, GDNF, Noggin, TGF3β	AA, BDFN, dcAMP, FGF2, GDNF, LMX1A, SHH, SMI	AA, BDNF, dcAMP, FGF8, GDNF, Noggin, SHH, SMI	AA, BDNF, CHIR, DATP, dbcAMP, FGF8, GDNF, Purmorphamine, SHH, SMI, TGF3β	AA, BDFN, dcAMP, FGF2, FGF8, GDNF, SHH, SMI	AA, BDNF, cAMP, FGF8, GDNF, Noggin, SHH, SMI, TGF3β	AA, BDNF, CHIR, dcAMP, FGF8, GDNF, PMA, SMI, TGF3β	FGF2, FGF8, SHH
Developmental markers (protein, mRNA)	Nestin	CDX2, FGF5, Nestin,OTX2, PLZF, PAX6, SOX1, SOX17	EN1, FOXA2, LMX1A, LMX1B, Nestin, PITX3, TAT, WNT1	FOXA2, Nestin, NURR1, PAX6	FOXA1, FOXA2, HESS, LHX2, LMX1A, NURR1, OTX2, PAX6	CRIPTO, NCAM, Nestin, PAX6, SOX1	DNMT3B, FOXA2, Nestin, PAX6	Brachyury, FOXA2, Nestin, PAX6, PAX7, SOX1, SOX9, TFAP2A	NURR1
Maturity markers (protein, mRNA)	GEPH, GluR1, MAP2, PSD95, SYN-1, TH, β-III-tubulin, VGAT, VGLUT1	TH, β-III-tubulin	MAP2, PITX3, TH	AADC, Calbindin, DAT1, GBA, GIRK2, IP3R, LRRK2, PITX3, α-synuclein, tau, TH	DAT, GIRK2, TH, β-III-tubulin	AADC, EN1, GFAP, MAP2, O4, PAX2, PAX5, SV2, SYN-1, TH, VMAT2	TH, β-III-tubulin	MAP2, PAX3, PAX7, TH, β-III-tubulin	ALDH1A1, GFAP, MAP2, PITX3, SCN1A, TH, β-III-tubulin, VMAT2
Physiological function	DA production, spontaneous Ca2+ oscillations, spontaneous EPSPs and IPSPs	ND	ND	DA production and uptake, spontaneous Ca2+ oscillations, mDA-specific mitochondrial responses, slow action potential trains	DA production, slow action potential trains and spontaneous spikes	DA production, repetitive action potential trains	DA production	Spontaneous action potentials	ND