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Table 2 Placebo-controlled stem cell applications in animal models of parkinsonism

From: Cell based therapy in Parkinsonism

Striatal MPTP and subcutaneous proteasome inhibitor (MG-132) lesioned animals

Authors animals

Product expanded allogenic ASCs Cyclosporin A

Applic/Observ time

Characteristics/Dosages/Application

Outcome(* = p < 0.05 / ** = p < 0.01 / *** = p < 0.001)

Chao, He et al. [54]

mMSCs

Directly after last MPTP injection/1 month

1. Intraperitoneal saline (n = 24)

• SN TH+ cells: 3** > 2

2. Intraperitoneal MPTP + IV saline (n = 24)

• SN microglial cells: 3* < 2

Male C57BL/6 mice

3. Intraperitoneal MPTP + IV 105 mMSCs (n = 24)

Phagocytosis and Complement inhibition: 3* < 2

Park, Bang et al. [62]

hiMSCs

1 day after last MPTP and 3-NP injection/28 days

1. Intraperitoneal saline-treated (n = 10)

• Group 2 and 3: 48% loss of nigral cells;

2. Intraperitoneal MPTP + 3-NP (n = 8)

• Group 3 compared to group 2:

Male C57BL/6 mice

  

3. Intraperitoneal MPTP + 3-NP and IV 1×106 hiMSCs in 200 μl (n = 8)

a. 2% of hiMSCs in SN, and 4% in the Striatum

b. Motor behavior improved* during 10 days

c. Increased modulation of cell survival* and decreased modulation of death-signaling** pathways, with 20% cell survival**

d. Decreased modulation of inflammation** and gliosis***, with a marked decrease of activated microglia** and astrocytes***

Bjugstad, Teng et al. [60]

hiNSCs

4 and/or 6 months after last MPTP injection/4 (n = 3) and 7 months (n = 4)

Bilateral intrastriatal and unilateral intranigral implantation of each 106 hiNSCs (n = 7) in the intramuscular MPTP lesioned monkey

• >80% of hiNSCs immigrated along the impaired nigrostriatal pathway

African green Monkeys

• < 1% of a total of 2x106 hiNSCs implanted within the caudate nucleus (intrastriatal) was identified at this site.

Park, Lee et al. [52]

hMSCs

21 days/3, 4, 6, 7, 10 weeks

1. MG-132 lesioned rats

• 1.7% hMSCs detected in the nigral substance

2. MG-132 lesioned rats treated during 3 weeks with weekly intravasal application of 106 hMSCs

• Survival of nigral and striatal TH+cells* after hMSCs

• Increased striatal dopamine level* after hMSCs

Male rats

• Reduction* in microglia activation after hMSCs

  1. Abbreviations: ASCs Adult stem cells, IV Intravenous, MPTP 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MSCs Mesenchymal stem cells, NSCs Neural stem cells, h human m mouse, i induced or transduced, MG-132 carbobenzoxy-Leu-Leu-leucinal, a proteasome inhibitor. SN Substantia Nigra, TH+ Tyrosine Hydroxylase Immunoreactive positive cells.