Differentiation Method Cell Type Results (In vitro/In vivo) References
Multi-stage method:
1) FGF-2 (7d)
2) FGF-8, SHH (7d)
3) BDNF (7d)
4) Astrocyte co-culture (5-12d)
Murine MAPC 25% efficiency of dopaminergic neuron
generation (IF); electrophysiological
characteristics similar to midbrain
Jiang et al. [24]
NICD transfection, FGF-2+CNTF+ FBS
+forskolin (5d), GDNF or BDNF+NGF
Human and rat MSCs 41% TH-positive (IF);
electrophysiological properties; DA
release after depolarization; functional
improvement in hemiparkin-sonian rats
Dezawa et al. [81]
Neurosphere formation with EGF+FGF-2
(2-10 weeks), BDNF (10-14d)
Human MSCs 11% TH-positive (IF); DA release after
depolarization; loss of osteogenic
differentiation capacity
Hermann et al. [25]
Neurosphere formation with
IBMX+forskolin+ TPA (3hrs), dbcAMP
Human MSCs 15% of β tubulin III-positive cells also
TH-positive (IF); lack of graft survival
and differentiation in PD model
Suon et al. [74]
IBMX (2d), GDNF+ IL-1β+mesencephalic
glial-conditioned med-ium+flash-frozen
mes-encephalic cell frag-ments (7-15d)
Rat MSCs 35% TH-positive (IF) Guo et al. [62]
Expansion (10% FBS+ DMEM; 3d),
neuron-conditioned medium alone (6-
9d), SHH+ FGF-8+neuron-condit-ioned
medium (3-12d)
Human MSCs from Wharton’s jelly of
umbil-ical cord
12.7% TH-positive (IF); DA secretion;
partial correction of amphetamineevoked
rotational behavior
Fu et al. [218]
CoCl2+Y-27632 (72hr) Murine MSCs TH expression; neurotransmitter
respons-iveness: glutamate (42%), DA
Pacary et al. [216]
SHH+FGF-8+FGF-2 (12d) Human MSCs 67% TH-positive (IF); synthesize and
constitutively secrete DA
Trzaska et al. [101]
FGF-2+EGF (48hr), BHA+dbcAMP+IBMX
+RA+GDNF (96hr)
Human MSCs TH protein expression; DA secretion;
31% TH-positive (flow cytometry)
Kan et al. [103]
FGF-2+EGF (48-72hr),
Human MSCs 30% TH-positive (flow cytometry); DA
secretion in response to depolarization
Barzilay et al. [219]
1) FGF-2 (7d)
2) SHH+FGF-8 (7d)
3) BDNF (7d)
Rat MSCs 60% β tubulin III-positive; none THpositive;
functional improvement in
hemiparkinsonian rats, but in both
control and neuronal-like MSCs
Bouchez et al. [208]
FGF-2+GDNF+10% calf serum (2wk) Human MSCs (PD-derived) 30% TH-positive (flow cytometry); DA
release after depolarization
Zhang et al. [220]
1) FGF-2+EGF (7d)
2) SHH+FGF-8+AA (7d)
3) GDNF+AA (7d)
Human MSCs 60-80% β tubulin III-positive; none THpositive;
transient survival of Stage 1
cells in lesioned hemisphere; microglial
and astroglial accumulation around graft
Khoo et al. [214]
d, days
IF, immunofluorescence staining
Table 1: In Vitro Dopaminergic Neuronal Differentiation of MSCs (cont’d).