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
neurons |
Jiang et al. [24] |
NICD transfection, FGF-2+CNTF+ FBS
+forskolin (5d), GDNF or BDNF+NGF
(7-11d) |
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
(7d) |
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
(76%) |
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),
dbcAMP+IBMX+AA+ or GDNF+(BDNF+RA TGF3+RA)(7d) |
Human MSCs |
30% TH-positive (flow cytometry); DA
secretion in response to depolarization |
Barzilay et al. [219] |
Multi-stage:
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] |
Multi-stage:
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