Effects of intravenous human umbilical cord blood CD34+ stem cell therapy versus levodopa in experimentally induced Parkinsonism in mice

静脉注射人脐带血 CD34+ 干细胞治疗与左旋多巴对小鼠实验性帕金森病的影响

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作者:Noha Abo-Grisha, Soha Essawy, Dina M Abo-Elmatty, Zenab Abdel-Hady

Conclusions

CD34+ cells ameliorated motor, biochemical and histological deficits in MPTP-parkinsonian mice, these effects were superior to those produced by levodopa that would be promising for the treatment of PD.

Material and methods

Mice were divided into 4 groups; saline-injected, MPTP: received four MPTP injections (20 mg/kg, i.p.) at 2 h intervals, MPTP groups treated with levodopa/carbidopa (100/10 mg/kg/twice/day for 28 days) or single intravenous injection of 10(6) CD34+ stem cells/mouse at day 7 and allowed to survive until the end of week 5.

Methods

Mice were divided into 4 groups; saline-injected, MPTP: received four MPTP injections (20 mg/kg, i.p.) at 2 h intervals, MPTP groups treated with levodopa/carbidopa (100/10 mg/kg/twice/day for 28 days) or single intravenous injection of 10(6) CD34+ stem cells/mouse at day 7 and allowed to survive until the end of week 5.

Results

Levodopa and stem cells improved MPTP-induced motor deficits; they abolished the difference in stride length, decreased percentage of foot slip errors and increased ambulation, activity factor and mobility duration in parkinsonian mice (p < 0.05). Further, they significantly (p < 0.05) increased striatal dopamine (85.3 ±4.3 and 110.6 ±5.3) and ATP levels (10.6 ±1.1 and 15.5 ±1.14) compared to MPTP (60.1 ±3.9 pmol/g and 3.6 ±0.09 mmol/g, respectively) (p < 0.05). Moreover, mitochondrial DNA from mice treated with levodopa or stem cells was in intact form; average concentration was (52.8 ±3.01 and 107.8 ±8.6) and no appreciable fragmentation of nuclear DNA was found compared to MPTP group. Regarding tyrosine hydroxylase (TH) immunostaining, stem cell group showed a marked increase of percentage of TH-immunopositive neurons (63.55 ±5.2) compared to both MPTP (37.6 ±3.1) and levodopa groups (41.6 ±3.5). Conclusions: CD34+ cells ameliorated motor, biochemical and histological deficits in MPTP-parkinsonian mice, these effects were superior to those produced by levodopa that would be promising for the treatment of PD.

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