Table 2 Mesenchymal stem cell transplantation in animal models of Huntington’s disease
Cells | Cell markers | Passage | Cell labeling | Cell number/inoculation site, inoculation time | Growth factor expression | Animal model/ age | Time of analysis | Animal behavior/ striatal volume | Cell distribution/ survival | Cell differentiation | Cell migratory activity | Conclusions and references |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
MSCs from mUCB | Positive: | Low: 3 to 8 | Hoechst 33,358 | 400,000 cells per hemisphere | mRNA: BDNF | R6/2, 5 weeks mice | Significant differences were observed between R6/2 and high-passage mUCB MSCs at 10 weeks of age | Not specified | No differentiation | Not specified | Transplantation of low-passage mUCB MSCs did not confer significant motor benefits. Limb-clasping was not observed [122] | |
CD45 | High: 40 to 50 | |||||||||||
SCA1 | ||||||||||||
SSEA4 | ||||||||||||
MHC class I | ||||||||||||
MHC Class II | ||||||||||||
rBM-MSCs | Not specified | Not specified | SPION | 5 × 105 or 1 × 106; striatum | Not specified | QA rat | 7 days after lesion | Not specified | Not specified | Not specified | Blood vessels and lateral ventricles in both hemispheres | Reduced brain damage and enhanced striatal expression of FGF-2 [125] |
rBM-MSCs | Not specified | Not specified | Hoechst 33,258 | 200,000 or 400,000 cells per hemisphere; 28 days after 3-NP | mRNA: BDNF, collagen type I and fibronectin | 3-NP rat | From 72 h to 14 days post-graft | Behavior improvements | No distribution | No differentiation | No migration | Increased mRNA:BDNF, collagen type I and fibronectin. Neuroprotective effect. Behavior improvement [126] |
Human AT-MSCs; hypoxia | Positive: nestin, NG2, KDR, FLT1, and CD34 | Not specified | Ad5-GFP | 5 × 105cells; bilateral striatum | mRNA: NGF, BDNF, bFGF, HGF, VEGF, IGF-1, GM-CSF, PDGF-α, EGF, CNTF | R6/2; 8.5 weeks mice | 4 weeks after injection | Slowed behavioral deterioration | Not specified | Tuj-1 GABAergic neurons. PGC-1α master regulator of mitochondrial biogenesis increased in ASC treated mice | Limited | Reduced striatal degeneration and formation of ubiquitin-positive aggregates. Behavior improvement [123] |
Negative: neurofilament O4 | ||||||||||||
Human AT-ASCs; hypoxia | Same as above | Not specified | Vybrant DiO | 106 cells; striatum after injection of QA | Same as above | QA mice; 8.5 weeks | Same as above | Significant improvement in apomorphine-induced rotation tests | Not specified | BDNF, calbindin, GABA, GAD—neuronal enzyme | Near transplantation locus forming a lump | Neuroprotective effect. Behavior improvement [123] |
Adult rBM-MSCs | Nestin+, GFAP+, SCF/c-kit+ | Passage ≥10 | PKH26, Hoechst and TOTO-3 | 100,000 cells; striatum | QA rat | 3 weeks or 8 weeks post-graft | Not specified | Significant | Undifferentiated | Limited; striatum | SCF increased expression [61] | |
Human BM-MSCs | Positive: CD29, CD44, CD49c, CD49f, CD59, CD90, CD105, CD166 | Early: 3 to 5 | GFP-hMSCs | 100,000 hMSCs; striatum | Not specified | N171-82Q mice | 1, 3, 5, 7, 15, and 30 days post-graft | Decreased atrophy of the striatal volume | Survival: 15.1 % at 24 h; 4.5 % at 5 days; 0 % at 15 days | hMSCs are undifferentiated. Endogenous cell: NeuN, βIII tubulin | hMSCs recruit pre-existing neuronal cells to the striatum | Increased: FGF-2, CNTF, VEGF, NGF. Endogenous cell proliferation. Reduced striatal degeneration [96] |
Negative: CD34, CD36, CD117, CD45 | ||||||||||||
Human BM-MSCs; immortalized cell line | Not specified | Not applied | Bisbenzimide + TOTO3 | 200,000 cells per hemisphere | Not specified | WT mice | 8 weeks post-graft | Not applied | Survival rate-significant | GFAP, DARPP-32 | Human BM-MSC transplantation induces migration of endogenous neuroblast cells | Not specified [124] |
Human BM-MSCs | Not specified | Not applied | 200,000 cells per hemisphere | Not specified | QA mice | 16 days post-graft | Improves: rotarod performance, striatum volume | Survival rate—significant. Reduced cell apoptosis | GFAP, NeuN, DARPP-32, F4/80 (macrophage and microglial marker) | Same as above | Neuroprotective effect. Behavior improvement. Reduced striatal degeneration [124] | |
Human BM-MSCs | Not specified | Not applied | 200,000 cells per hemisphere | Not specified | R6/2-J2 mice | 16 days post-graft | Improves: rotarod performance, striatum volume | Survival rate—significant. Reduced cell apoptosis | GFAP, NeuN, DARPP-32, F4/80 | Same as above | Same as above [124] |