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Table 1 Placebo-controlled stem cell applications in rodent animal models of parkinsonism

From: Cell based therapy in 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
  1. Abbreviations: 6-OHDA 6 hydroxydopamine, ASCs Adult stem cells, MSCs Mesenchymal stem cells, NSCs Neural stem cells, h human r rat, i induced or transduced, EGFP Enhanced Green Fluorescent Protein, BDNF Brain-Derived Neurotrophic Factor, GDNF Glial cell Derived Neurotrophic Factor, NT-3 Neurotrophine-3, P Pharmacologically active microcarriers, Bcl-X L anti-apoptotic granulocyte-colony stimulating factor enhancing the expression of key genes involved in dopaminergic patterning, differentiation and maturation); SNc Substantia Nigra pars compacta, TH+ Tyrosine Hydroxylase Immunoreactive positive cells.