Table 1.

Studies of grafts of PSCs into rodent striatum.

Protocol	Cell source	Host treatment	Transplant	Brief summary of results
Dinsmore et al. (1996)	mESC (E14TG2a; D3)	QA lesioned rat striatum Daily cyclosporine	100,000–1,000,000 cells. Survival up to 6 wk	Treatment of pluripotent ES cell cultures with retinoic acid (RA) induced populations of GABAergic expressing neurons (no specific neuronal type was targeted). Grafts containing 100,000 cells produced biggest grafts. Grafts stained positively for AChE, Thy1.2, TUJ1, NSE and GABA. No neurite outgrowth was determined due to the absence of a species specific marker.
Kallur et al. (2006)	NSCs from primary striatal tissue expanded in vitro as neurospheres	Intact striatum of neonatal rat (2–3 days) No immune suppression	100,000 cells Survival 4 and 16 wk	At 4 months 6–10% of cells had survived, the majority were located in the striatum but some had migrated to the GP, cortex or corpus callosum. At 4 months, the number of NESTIN positive cells had decreased whereas the number of DCX and NEUN cells had increased compared to at 1 month. Some cells were GFAP positive and the majority of all neurons stained positively for parvalbumin. A selection of neurons had morphology characteristic of mature neurons with long branching processes and visible dendritic spines whereas others had more astrocyte/oligodendrocyte like morphology.
Joannides et al. (2007a)	H9; HUES9	QA lesioned rat striatum Daily cyclosporine	100,000–250,000 cells Survival at 6 wk	Cells grown under optimized and fully defined human neuralizing medium under substrate-free conditions. No tumors evident following transplantation. Doublecortin (DCX) and NeuN positive neurons identified. Limited GFAP staining also evident- suggestive of some astrocyte differentiation. No DARPP-32 present, no sign of neuron migration from graft core.
Song et al. (2007)	Miz-hESC1	QA lesioned rat striatum Daily cyclosporine	20,000 cells Survival at 3 wk	Some cells migrated to the cortex and formed “aggregates” that were Nestin positive/NeuN negative. Some cells were GFAP positive. Cells remaining in the striatum migrated to the lesion core and were DCX and GAD67 positive/DARPP-32 negative. Improved apomorphine rotations at 1, 2 and 3 weeks compared to sham group. No overgrowth reported.
Aubry et al. (2008)	SA-01 (H9)	QA lesioned striatum in nude rat No immune suppression	50,000–200,000 cells Survival 4–6 wk	Grafts from “early” stage cells (day 21–30 of the protocol) showed no DARPP-32 expressing cells and developed “teratoma-like regions” whilst cells grafted from the “later” stage (day 46–59) of the protocol showed clusters of DARPP-32 (21% of NeuN positive neurons)/AChE negative cells and contained P-zones. The cells had medium sized bodies (10–16 µm), were bi-polar and showed extensive neurite outgrowth. There was overgrowth 13–15 weeks after the graft. No functional assessment.
Lee et al. (2009)	Adipose-derived stem cells (ASCs)	QA lesioned rat striatum Daily cyclosporine	100,000 cells	Grafts reduced apomorphine-induced rotations (1–4 weeks after), lesion volume, and striatal apoptosis.
		60 day old R6/2 mouse Daily cyclosporine	500,000 cells	Grafts improved rotarod performance and limb clasping, increased survival, attenuated the loss of striatal neurons, and reduced the Htt+ aggregates. Cells expressed DCX, TUJ1 and GAD.
Nasonkin et al. (2009)	hESCs (BG01)	Unlesioned Striatum in nude rats No immune suppression	15,000 cells Survival 1.5, 3 and 6 mo.	Following transplantation nestin and DCX expression decreased and TUJ1 increased. DARPP-32, calretinin and parvalbumin expression at 6 months, no GAD67. Synaptophysin evident and sparse Glur2/3. Axonal projections to the GPe and sub thalamic nucleus seen. No overgrowth, no functional assessment.
Vazey et al. (2010)	ENVY (GFP-expressing)	QA lesioned rat striatum Daily cyclosporine	75,000 cells Survival 4 and 8 wk	Grafted cells expressed MAP2 and NeuN at both time points, no DARPP-32 or GAD67. Overgrowth seen in 1 graft at 8 weeks. No functional assessment.
Ma et al. (2012)	hESCs	QA lesioned striatum in SCID mice No immune suppression	100,000 cells Survival 16 wk	Shorter protocol than previous attempts to generate LGE neural precursors that predominately differentiated into DARPP-32-expressing neurons. Cells were grafted after 40 days in vitro and 4 months after transplantation showed no over-growth and were positive for DARPP-32, MEIS2, CTIP2, enkephalin and substance P. Cells were multipolar, branched and had numerous dendritic buttons revealed through synaptophysin staining. Small populations of the neurons also expressed ChAT, vGLUT1, 5-HT, TH and calbindin. Functional recovery was seen on the rotarod and through an increase in stride length which was attributed to the host cortical and nigral inputs to the grafts as well as the projections afforded to the SN from the grafts.
El-Akabawy et al. (2012)	cmyc-ERTAM hNSC (STROC05)	R6/2 HD mouse No immune suppression	75,000 cells Survival up to 6 wk	Tested on a battery of behavior tests including rotarod, Cells did not diminish disease progression, possibly due to the short life span of the mouse (16 weeks). There was no DARPP-32. There was no sign of graft rejection but this does not rule out an early immune response on the graft.
Delli Carri et al. (2013)	hESCs (H9 and HS401)	QA lesioned rat striatum Daily cyclosporine	500,00 cells Survival at 3, 6 and 9 wk	Used the same concentration of SHH as Ma et al., to induce a ventral telencephalic identity and characterized extensively to ensure LGE precursors. Cells grafted at Day 38 of the protocol. At 6 and 9 weeks MAP2ab mad TUJ1 positive neurons were seen. At 9 weeks post-transplant FOXP1, FOXP2 and DARPP-32 staining was found in the grafts but not quantified. Projection of Nestin fibers into the intact striatum showed integration between host and graft. Amphetamine-induced rotations were compared before and after grafting from 3 weeks and results hinted at functional recovery, however animal numbers were too low to suggest a significant behavioral effect.
Nicoleau et al. (2013)	hESCs (H9)	QA lesioned striatum of nude rats. No immune suppression	100,000 cells Survival at 5 mo.	Optimized concentration of SHH and WNT signaling to produce human ventral telencephalic precursors that were characterized extensively before grating. Day 25 differentiated hESC grafted, DARPP-32 and FOXP1 found in grafts, as yet no behavioral assessment has been carried out.
Arber et al. (in press)	hESCs (H7) Activin protocol	QA lesioned rat striatum Daily cyclosporine	500,000 cells Survival at 4–16 wk.	DARPP-32 shown in grafts at 16 weeks containing CTIP2, FOXP2 and calbindin positive neurons. No overgrowth.