Table 1 Placebo-controlled stem cell applications in rodent animal models of parkinsonism
Striatal 6-OHDA lesioned rats | ||||
|---|---|---|---|---|
Authors animals (Sprague–Dawley rats) | Product expanded allogenic ASCs Cyclosporin A | Applic/Observ time | Characteristics/Dosages/Application | Outcome (* = p < 0.05/** = p < 0.01/*** = p < 0.001) |
Bouchez, Sensebe et al. [51] | rMSCs | 14/35 days | 1. No intervention (n = 6) | • Rotational behavior (turns/min) |
2. Intrastriatal saline (n = 7) | 1. No-intervention group: 23.8 ± 2.1 | |||
3. Intrastriatal 1.8×105 rMSCs (n = 7) | 2. Control saline-treated group: 25.1 ± 1.7 | |||
Female rats | riMSCs |  | 4. Intrastriatal 1.8×105 riMSCs (n = 7) | 3. MSC-treated group: 14.1 ± 3.3* |
4. Enriched rMSC-treated group: 10.8 ± 1.7* | ||||
• TH-positive neurons: | ||||
1. No-intervention group: 24.2 ± 6.7% | ||||
4. Enriched riMSC-treated group: 52.5 ± 8.2%* | ||||
Wang, Yasuhara et al. [32] | Fibroblasts | 2 hr/28 days | 1. Intravenous saline (n = 7) | • Amphetamine-induced rotational behavior |
2. Intravenous 107 fibroblasts (n = 6) | 1. Control group: 8.5 ± 3.5 turns/min | |||
Female rats | rMSCs | 3. Intravenous 107 rMSCs (n = 6) | 2. Fibroblast group: 8.2 ± 3.3 turns/min | |
3. rMSC group: 1.2 ± 0.7 turns/min* | ||||
• Cylinder test | ||||
1. Control group: 64.7 ± 17.3% | ||||
2. Fibroblast group: 60.2 ± 16.1% | ||||
3. rMSC group: 29.3 ± 13.7%* | ||||
• Preservation of TH+cells: 3* > 2 > 1 | ||||
Danielyan, Schafer et al. [53] | rMSCs (EGFP labeled) | 7,9/110–136 days | Intranasal saline day 7 and 9 (n = 7) | • Stepping ratio (contralateral/ipsilateral) MSC-treated group 2 (0.7)** > group 1 (0.1) |
1. Intranasal 5x105 MSC day 7 and 9 (n = 9) | • Amphetamine-induced rotational behavior | |||
MSC-treated group 4* < group 3 | ||||
Female rats | 2. Intranasal saline day 7 and 9 (n = 10) | • Histology | ||
Intranasal 5×105 MSC day 7 and 9 (n = 12). | a. Group 4: 24% of MSCs survived in central nervous system for at least 4.5 months | |||
b. TH+ cell survival: Group 2* > 1 and 4* > 3 | ||||
c. Inflammatory cytokines Group 2* < 1 and 4* < 3 | ||||
Blandini, Cova et al. [58] | hMSCs | 5/28 days | 1. Intrastriatal saline (n = 9) | • Apomorphine-induced rotational behavior |
Male rats | 2. Intrastriatal 1×105 hMSCs (n = 8) | 1. No effect | ||
2. Reduced rotational behavior* | ||||
• Expression of GDNF increased in hMSCs group | ||||
• Apoptosis decreased in hMSCs treated group | ||||
Cova, Armentero et al. [57] | hMSCs | 5/28 days | SHAM unilateral lesion | • Dose-dependent neurorescue effects (hMSCs vs saline) in unilateral 6-OHDA lesioned, but not SHAM lesioned, rats with |
1.Intrastriatal saline | ||||
2. Intrastriatal 3.2×104 hMSCs (n = 6-10) | ||||
Male rats | 3. Intrastriatal 1.8×105 hMSCs (n = 6-10) | a) Reduction*/** ongoing toxin-induced degeneration of dopaminergic terminals | ||
6-OHDA unilateral lesion | ||||
1. Intrastriatal saline | b) Enhanced neurogenesis*/** (neural progenitor cells) in the periventricular zone | |||
2. Intrastriatal 3.2×104 hMSCs (n = 6-10) | ||||
3. Intrastriatal 1.8×105 hMSCs (n = 6-10) | c) Persistent release of specific cytokines | |||
Delcroix, Garbayo et al. [37] | rMSCs | 14/64 days | 1. Intrastriatal saline (n = 6) | • Rotational behavior (turns/min): |
2. Intrastriatal 1.5×105 rMSCs (n = 6) | 1. saline treated group: 18.5 | |||
3. Intrastriatal 1.5×105 riMSCs + P (n = 6) | 2. rMSCs-treated group: 17.5 | |||
Female rats | riMSCs | 4. Intrastriatal 1.5×105 riMSCs + P + NT3 (n = 6) | 3. riMSCs + P treated group: 8.5* | |
4. riMSCs + P + NT3 treated group: 3.0* | ||||
riMSCs + P | • Preservation of TH+cells : 4* > 3 > 2 > 1 | |||
Levy, Bahat-Stroomza et al. [56] Male rats | hMSCs | 35/125 days | 1) Intrastriatal saline in 5 (n = 7) | • Rotational behavior (turns/min) (post-lesional 100%) |
hiMSCs (neural phenotype) | 2) Intrastriat. 5×105 MSC’s (n = 7) | 1) saline-treated group: 88% | ||
3) Intrastriat. 5×105 neural iMSC’s (n = 7) | 2) hMSCs-treated group: 90% | |||
3) hiMSCs-treated group: 42%* | ||||
Sadan, Bahat-Stromza et al. [55] | hMSCs | 1 hr/42 days | 1) Intrastriatal saline (n = 10) | • D-amphetamine-induced rotational behavior |
Male rats | hiMSCs (BDNF/GDNF) | 2) Intrastriatal 1.5 or 4.5×105 hMSCs (n = 21) | 1. saline group: increase 4.74 ± 1.07 turns/min | |
2. MSCs group: increase 2.86 ± 0.54 turns/min | ||||
3. Intrastriatal 1.5 or 4.5×105 hiMSCs (n = 21) | 3. iMSCs group: increase 2.16 ± 0.37* turns/min | |||
• TH-positive area (treated versus untreated site) | ||||
2. hMSCs group: treated site > untreated site | ||||
3. hiMSCs group: treated site* > untreated site | ||||
Zhu, Ma et al. [59] Male rats | rNSCs | 35/155 days | 1. No intervention (n = 13) | • Rotational behavior: |
2. Intranigral(SNc) 5×104 rNSCs (n = 20) | 1. Group without intervention: 233.9 ± 70.43 | |||
3. Intrastriatal 5×104 rNSCs (n = 5) | 2. rNSCs SNc group:189.3 ± 63.24*** | |||
3. rNSCs Intrastriatal group: 169.3 ± 47.28* | ||||
• TH-positive cells in the SNc: 2 > 1 | ||||
• EGFP-labeled NSCs identified as TH+cells in 2 and 3 | ||||
Ramos-Moreno, Castillo et al. [61] Female rats | hNSCs | 45/165 days | 1. Intrastriatal saline (n = 15) | • D-amphetamine-induced rotational behavior: |
hiNSCs |  | 2. Intrastriatal 3×105 hNSCs (n = 17) | 1. Control group: 18 turns/min | |
(expressing Bcl-XL) |  | 3. Intrastriatal 3×105 hiNSCs Bcl-XL expression (n = 21) | 2. hNSCs-treated group:17 turns/min | |
3. hiNSCs-treated group: 3 turns/min*** | ||||
• Apomorphine-induced rotational behavior: | ||||
1. Control group: 6.5 turns/min | ||||
2. hNSCs-treated group: 2 turns/min** | ||||
3. hiNSCs-treated group: 2.5/min** | ||||
• Paw mobility test: 3** > 2* > 1 | ||||