Table 1.

Mesenchymal stem cell transplantation in Huntington’s disease.

Study (year)	Animal model	Type of cell	Behavioral outcome	Histology	Trophic support	Time course	Immunosuppression	Transplantation	Ref.
Mouse animal model
Dey et al. (2010)	YAC128 Mouse	Genetically engineered mouse bone marrow MSCs	YAC128 mice receiving bone marrow transplants demonstrated reduced clasping behavior and longer latencies on the rotarod task	YAC128 mice receiving grafts had significantly more NeuN-positive cells in the striatum compared with untreated YAC128 mice	BDNF-engineered Cells had greater behavioral and histological recovery than NGF- or non-engineered cells	Cells were not observed at the conclusion of study, but behavioral and histological effects were still observed	None	Allogeneic	[39]
Im et al. (2010)	YAC128 mouse	HD Human adipose MSC	YAC128 mice receiving cell transplants showed a delay in motor deficits up to 4 weeks (measured on the rotarod) following transplantation	Normal adipose cells were able to reduce striatal atrophy while HD adipose cells were unable to prevent atrophy	Cells expressed BDNF in vitro	Cells transplanted at 8 or 12 months old. Cells were not detectable 4 months post-transplantation	None	Xenogeneic (hMSC)	[43]
Lee et al. (2009)	R6/2 mouse	Human adipose MSC	In R6/2 mice receiving transplants, there was increased life-span, rotarod performance and decreased limb clasping	Grafted R6/2 mice showed a decrease of striatal neuron loss and reduced huntingtin aggregation	Adipose stem Cells secreted BDNF, believed to be mechanism of recovery	Cells transplanted at 8 weeks tested for four additional weeks (approximately 13.5% cell survival). Behavioral effects seen after 2 weeks post-operation	None	Xenogeneic (hMSC)	[44]
Fink et al. (2013)	R6/2 mouse	mouse umbilical cord-derived MSC	Transient behavioral sparing was observed following transplantation	MSC transplantation significantly reduced striatal atrophy	UC MSC expressed BDNF in vitro and was speculated to promote neuropathological sparing	MSCs survived 6 weeks post-transplantation	None	Allogeneic	[41]
Rossignol et al. (2015)	R6/2 mouse	Mouse bone marrow MSC	Delay in the onset of motor and cognitive deficits in rotarod, clasping and Morris Water Maze	MSC transplantation significantly reduced striatal atrophy	MSC transplantation upregulated expression of BDNF in vivo.	MSCs survived 6 weeks post-transplantation	None	Allogeneic	[40]
Lin et al. (2009)	QA Mouse model, R6/2 mouse model	hMSCs	QA mice receiving MSC transplants demonstrated significant motor recovery on the rotarod task and increased the survivability of the mice	QA mice receiving transplants showed partial striatal recovery in terms of striatal volume	MSC improved neuronal differentiation, motor deficits and cell loss through trophic support	Small number of cells survived up to 8 weeks and could induce endogenous cell proliferation up to 16 weeks	None	Xenogeneic (hMSC)	[45]
Snyder et al. (2012)	N171–82Q (knockin) mouse	hMSCs	No behavioral analysis was performed	Human MSCs were rapidly rejected from the host. However, mice receiving transplants had increased proliferation and neural differentiation of endogenous stem cells. Mice receiving grafts also displayed decreased striatal atrophy and increased neurotrophic signaling	Transplanted MSC stimulated neurotrophic signaling	Transplanted human MSC disappeared over 15 days; however, endogenous cell proliferation, neural differentiation, neurotrophic signaling and decreased atrophy persisted up to 30 days	Cyclosporine A	Xenogeneic (hMSC)	[47]
Rat animal model
Sadan et al. (2008)	QA rat model	Rat MSCs	No behavioral analysis was performed	Cells were capable of migrating toward the lesion site and aided in decreasing the lesion volume	BDNF was the main contributor for migration to lesion site	Cells survived for 19 days in vivo	None	Allogeneic	[37]
Lescaudron et al. (2003)	QA rat model	Rat whole bone marrow	QA rats receiving bone marrow transplants demonstrated a reduction of cognitive deficits in the radial arm water maze when compared with untreated QA rats	No neuronal differentiation of transplanted cells	Behavioral recovery was speculated to be due to BDNF release	Tested 10 days following bone marrow administration	None	Autologous	[33]
Lee et al. (2009)	QA rat model	Human adipose MSC	In QA rats receiving adipose stem cells, there was a reduction in apomophine-induced rotation behavior	Grafted QA rats had decreased lesion volume and striatal apoptosis	Adipose stem cells secreted BDNF, believed to be mechanism of recovery	Cells transplanted at 8 weeks tested for 4 additional weeks (approximately 13.5% cell survival). Behavioral effects seen after 2 weeks post-operation	None	Xenogeneic (hMSC)	[44]
Edalatmanesh et al. (2010)	QA rat model	Rat bone marrow MSCs	In QA rats receiving MSCs, there was a reduction in apomophine-induced rotation behavior, increased performance in the cylinder test, improvement of motor function as measured by beam walking and hanging wire test and memory improvement as measured in the Morris Water Maze when compared with untreated animals	Histological analysis was not performed	Recovery was speculated to be due to the release of neurotrophic factors, specifically BDNF	Cells transplanted 1 week post QA lesion, behavior testing performed one week following transplantation. Behavioral sparing observed immediately	None	Allogeneic	[48]
Jiang et al. (2010)	QA rat model	Rat bone marrow MSCs	Rats receiving transplants exhibited reduced apomorphine-induced rotational behavior and longer latencies on the rotarod when compared with untreated animals	Grafted cells survived for 8 weeks, significantly reduced the amount of striatal loss observed and elevated the levels of NGF, BDNF, GDNF and CNTF in the brain	Behavioral recovery due to the release of neurotrophic factors, including BDNF	Cells, transplanted 1 week following QA lesion, were detectable for 2 weeks; however, few cells were observed at 8 weeks post	None	Allogeneic	[34]
Sadan et al.(2010)	QA rat model	Neurotrophic-factor-treated hMSCs	Reduction in apomorphine-induced rotations	Grafted cells survived for 42 days and reduced lesion size	Neurotrophic factor secreting cells reduce lesion size and behavior abnormalities	Neurotrophic factortreated MSCs (specifically BDNF) survived better than nontreated cells	Cyclosporin A	Allogeneic	[46]
Serrano Sánchez et al. (2014)	QA rat	Rat bone marrow MSC	None performed	Significant reductions of BDNF levels in the cortex and striatum following lesion	MSC transplantation increased brain BDNF levels	MSC transplanted 4 weeks following QA lesion. BDNF levels were measured 30 days posttransplantation and were elevated in the group receiving MSC	None	Allogeneic	[38]
Hosseini et al. (2015)	QA rat	Human adipose MSC	Improvement in rotarod, hanging wire, reduced apomophine-induced rotations and reduction in anxiety-like behaviors	Cells survived for at least 7 weeks in the brain	Recovery was speculated to be due to the release of neurotrophic factors	Rats were transplanted 7 days following QA lesion. Behavioral testing was conducted over a 10-week period	None	Xenogeneic (hMSC)	[42]
Rossignol et al. (2011)	3-NP rat model	Rat bone marrow MSCs	3-NP rats receiving transplants showed reduction of deficits in paw placement, stepping test and hindlimb retraction when compared with untreated animals	Trend toward lesion size reduction in rats receiving transplant. No neuronal differentiation of transplanted cells	Behavioral and histological recovery thought to be due to increase of BDNF immunoreactivity in the area around the transplant	Small transplants were observed 72 days post-transplantation	None	Allogeneic	[35]
Rossignol et al. (2013)	tgHD rat	Rat bone marrow MSC and aNSC	Co-transplantation of MSC and aNSC reduced motor dysfunction as measured on the Accelerod	MSC significantly increased aNSC graft survival	MSC likely secreted trophic support and created a local immunomodulatory environment in the striatum	MSCs survived up to 12 weeks post-transplantation	None	Allogeneic	[36]

aNSC: Adult neural stem cell; HD: Huntingdon’s disease, hMSC: Human bone marrow mesenchymal stem cell; MSC: Mesenchymal stem cell; QA: Quinolinic acid; tp :transplantation.