Table 3.
Cell transplantation in Huntington’s disease.
| Study (year) | Animal model | Type of cell | Behavioral outcome | Histology | Ref. |
|---|---|---|---|---|---|
| Mouse animal model | |||||
| Yang & Yu (2009) | R6/2 mouse | Mouse NSCs | R6/2 mice receiving cells had increased life spans and improved motor function on the beam walking and rotarod task when compared with untreated animals | NSCs transplanted into R6/2 mice differentiated into neurons, reduced striatal loss and reduced ubiquitin-positive aggregation in the striatum | [126] |
| Dunnett et al. (1998) | R6/2 mouse | Mouse lateral ganglionic eminence | R6/2 mice receiving transplants demonstrated increased locomotion in the open field test | Grafts were capable of survival, integration and differentiation into neurons | [119] |
| Yang & Yu (2009) | R6/2 mouse | Mouse NSCs | R6/2 mice receiving cells had increased life spans and improved motor function on the beam walking and rotarod task when compared with untreated animals | NSCs transplanted into R6/2 mice differentiated into neurons, reduced striatal loss and reduced ubiquitin-positive aggregation in the striatum | [126] |
| Johann et al. (2007) | QA mouse model, R6/2 mouse | Mouse embryonic NSCs | No behavioral analysis was performed | Cells differentiated into astrocytes and were rejected after 14 (QA mouse) and 28 days (R6/2) | [131] |
| Bernreuther et al.(2006) | QA mouse model | Mouse ESCs | Mice receiving transplants of cells exhibited reduced amphetamine-induced rotational behavior when compared with untreated animals up to 4 weeks following surgery, but returned to sham levels at 8 weeks | Transplanted mice showed an increase in the number of neurons in the striatum and differentiated into astrocytes and GABAergic neurons | [121] |
| Pineda et al. (2007) | QA mouse model | Genetically engineered mouse NSCs | Mice receiving transplants of cells exhibited reduced amphetamine-induced rotational behavior when compared with untreated animals | Cells were able to survive and proliferate in the mouse brain. Mice receiving transplants showed less striatal loss when compared with untreated animals | [129] |
| Shin et al. (2012) | QA mouse model | Mouse embryonic NSCs | No behavioral analysis was performed | Grafted cells survived for 28 days and differentiated into mature neurons expressing DARPP32 | [133] |
| Rat animal model | |||||
| Aubry et al. (2008) | QA rat model | Striatal progenitors derived from human ESCs | No behavioral analysis was performed. | Cells transplanted at the ganglionic eminence stage were capable of survival,differentiation into striatal neurons, but resulted in tumor-like overproliferation | [122] |
| Song et al. (2007) | QA rat model | Human ESC neural precursors | Rats receiving transplants exhibited reduced apomorhine-induced rotational behavior when compared with untreated animals | Cells were positive for early neuronal markers and no tumor formation was observed at 3 weeks post-transplantation | [130] |
| Kordower et al. (1997) | QA rat model | Genetically engineered mouse embryonic NSCs | No behavioral analysis was performed | Rats receiving grafts displayed sparing of striatal neurons after QA injection | [134] |
| Hurlbert et al. (1999) | QA rat model | Human teratocarcinoma neural precursors | Rats receiving transplants exhibited reduced methamphetamine-induced rotational behavior and improved forelimb use in a staircase task when compared with untreated animals | Cells survived for 12 weeks and displayed markers of mature neurons but did not differentiate into medium spiny neurons (DARPP32) | [135] |
| Armstrong et al. (2000) | QA rat model | Rat embryonic NSCs | No behavioral analysis was performed | Grafted cells survived for 12 weeks following surgery and some differentiated into mature phenotypes expressing DARPP32. It was also observed that grafts exhibited neuronal fibers outgrowth | [136] |
| Vazey et al. (2006) | QA rat model | Rat adult NSCs | Rats receiving transplants exhibited reduced apomorhine-induced rotational behavior and increased forelimb exploratory behavior when compared with untreated animals | Cells survived for up to 8 weeks following surgery, migrated throughout the striatum and differentiated into astrocytes, mature neurons and striatal medium spiny neurons | [127] |
| Visnyei et al. (2006) | QA rat model | Rat embryonic NSCs | No behavioral recovery was observed in QA rats receiving cells in apomorphine-induced rotation tests | Cells survived, migrated toward the lesion site and olfactory bulbs and differentiated into astrocytes and neurons | [137] |
| Bosch et al. (2004) | QA rat model | Immortalized NSCs | Rats receiving transplants exhibited reduced apomorhine-induced rotational behavior when compared with untreated animals | Transplanted cells maintained a GABAergic phenotype, had elaborate neurite processes and formed synaptic connections with endogenous neurons | [128] |
| Ryu et al. (2004) | 3-NP rat model | Immortalized human embryonic NSCs | Rats that received cell transplantation prior to administration of 3-NP demonstrated improved motor function on a rotarod task when compared with 3-NP animals not receiving cells | Transplanted cells expressed primarily immature neuronal markers with few cells expressing intermediate neurons or astrocytes | [120] |
3-NP: 3-nitropropionic acid; ESC: Embryonic stem cell; NSC:Nueral stem cell; QA: Quinolinic acid.