Human induced pluripotent stem cell–derived neurons improve motor asymmetry in a 6-hydroxydopamine–induced rat model of Parkinson's disease

Han, Fabin; Wang, Wei; Chen, Baoxing; Chen, Chao; Li, Sen; Lu, Xianjie; Duan, Jing; Zhang, Yang; Zhang, Yu Alex; Guo, Wennian; Li, Guangyao

doi:10.1016/j.jcyt.2015.02.001

Cited by 70 publications

(62 citation statements)

References 44 publications

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“…52,53 We studied the effect of transplantation of the induced pluripotent stem cells and the human umbilical blood-derived stem cells to PD or AD animal models in our laboratory and found a significant symptomatic recovery. 54,55 In future, we would also like to combine the transplantation of stem cells and coinjection of ephrin-A1 and PDGF-BB to cure the neurodegenerative disease in PD and AD animal models.…”

mentioning

confidence: 99%

Direct interaction of receptor tyrosine kinases, EphA4 and PDGFRβ, plays an important role in the proliferation of neural stem cells

Chen¹,

Sawada²,

Sakaguchi³

et al. 2017

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Abstract:Receptor tyrosine kinases mediate the extracellular signals and transmit them into the cytoplasm by activating intracellular proteins through tyrosine phosphorylation. Both Ephs and platelet-derived growth factor (PDGF) receptors (PDGFRs) have been implicated in neurogenesis, but the functional interaction between these two pathways is poorly understood. Here, we demonstrated that EphA4 directly interacts with PDGFRβ and mutually activates each other when expressed in HEK293T cells. H9-derived neural stem cells express Ephs and PDGFRs, and their proliferation is stimulated by ephrin-A1 and PDGF-BB with further augmentation by their combined application. As both EphA4 and PDGFRβ play important roles in preventing neurodegeneration and promoting neuroprotection, their interaction and transactivation might transduce the signal through the EphA4/PDGFRβ complex and augment the proliferation of neural stem cells.

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mentioning

confidence: 99%

Direct interaction of receptor tyrosine kinases, EphA4 and PDGFRβ, plays an important role in the proliferation of neural stem cells

Chen¹,

Sawada²,

Sakaguchi³

et al. 2017

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“…In addition, preclinical studies also found the safety and efficacy of the human unfertilized cell or induced pluripotent stem cells. These later cells have been found to improve the motor symptoms of PD in the animals [21,26]. Similarly, in a 14 year study it was observed that most of the transplanted dopaminergic neurons remained functional and [27].…”

Section: Cell Based Therapies For Pdmentioning

confidence: 79%

“…This technique reduced the dosage requirement of anti-PD drugs. Additionally, they improve the motor signs of PD [18][19][20][21]. Some of the early studies found that the formation of tumor after embryonic stem cell transplantation is a major drawback of this technique [22,23].…”

Section: Cell Based Therapies For Pdmentioning

confidence: 99%

The role of cell based therapy in the treatment of Parkinson’s disease

Habibyar¹

2017

J Syst Integr Neurosci

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Parkinson's disease (PD) is considered to be the second common neurodegenerative illness after Alzheimer's disease worldwide. It affects 1-2% of the world population. PD is associated with motor symptoms such as bardykinesia, resting tremor, muscle rigidity. Additionally, non-motor symptoms of PD include sleep disturbance, depression and postural instability. These all PD symptoms are attributed to the selective and progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. A number of pharmacological agents are today available for the treatment of PD. These medications are associated with adverse drug events or lack of efficacy in some patients. Therefore it is required to explore novel methods for the treatment of PD i.e., cell based therapy. A number of cell based therapeutics is tried for the treatment of PD such as embryonic stem cells, induced pluripotent stem cells and somatic stem cells. Although this novel method proved to be effective in PD treatment in animal and clinical studies. But on the other hand it leads to the worsening of the non-motor symptoms. Thus, these studies are not enough, more long term clinical trials are required to proof the efficacy of all aspects of PD through cell based therapy including non-motor symptoms.

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“…By reading the full text of the remaining 125 articles carefully, 16 studies were excluded due to not having unsorted iPSC experiments; 28 studies were excluded because there was no PD model; 54 were excluded because in vivo testing had not been performed; 12 studies were removed because the animal model was impertinent; and one was published after March 2017. Therefore, eight studies (16,17,(20)(21)(22)(23)(24)(25) met the eligibility criteria and were included in the meta-analyses. The systematic search to identify all articles for the meta-analysis is presented in Fig.…”

Section: Study Inclusionmentioning

confidence: 99%

“…2). For apomorphine-induced rotation tests, similarly, one study (24) was excluded from the pooled analysis due to the data being represented in the form of a ratio and one study (16) did not describe the outcome in detail; therefore, it was not possible to calculate the mean and SD. Thus only three experiments (21,25) were reported for evaluating the effect of iPSCs on apomorphine-induced rotation tests.…”

Section: Efficacy Of Ipscsmentioning

confidence: 99%

Induced pluripotent stem cells in rat models of Parkinson's disease: A systematic review and meta‑analysis

Zhang

Qin

et al. 2018

biom rep

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Abstract. The effects of induced pluripotent stem cells (iPSCs) in 6-hydroxydopamine-lesioned rat models of Parkinson's disease (PD) have been evaluated in multiple studies. However, the results evaluating the effectiveness of iPSCs in animal models of PD are mixed, primarily due to their low statistical power. In the current study, a meta-analysis was performed to describe the treatment effect of unsorted iPSCs on behavioral testing in experimental rat models of PD. Databases searched included PubMed, EMBASE, MEDLINE and the Cochrane Library from inception to March 2017. Data were extracted for rotation behavior tests (induced by amphetamine and apomorphine) and limb function tests. A total of eight studies were included in the current meta-analysis, and iPSCs were identified to be efficacious according to the pooled standardized mean differences (SMDs) for improving amphetamine-induced rotational behavior [SMD, -2.16; 95% confidence interval (95% CI), -2.93, -1.40; P<0.00001] and apomorphine-induced rotational test (SMD, -1.45; 95% CI, -2.16, -0.73; P<0.0001). The pooled evidence indicated that iPSCs improve rotational behavior in rat models of PD. It was concluded that iPSCs provide a potential approach for developing novel treatment strategies for PD, and the results of this meta-analysis may guide future preclinical and clinical studies.

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Human induced pluripotent stem cell–derived neurons improve motor asymmetry in a 6-hydroxydopamine–induced rat model of Parkinson's disease

Cited by 70 publications

References 44 publications

Direct interaction of receptor tyrosine kinases, EphA4 and PDGFRβ, plays an important role in the proliferation of neural stem cells

Direct interaction of receptor tyrosine kinases, EphA4 and PDGFRβ, plays an important role in the proliferation of neural stem cells

The role of cell based therapy in the treatment of Parkinson’s disease

Induced pluripotent stem cells in rat models of Parkinson's disease: A systematic review and meta‑analysis

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Human induced pluripotent stem cell–derived neurons improve motor asymmetry in a 6-hydroxydopamine–induced rat model of Parkinson's disease

Cited by 70 publications

References 44 publications

Direct interaction of receptor tyrosine kinases, EphA4 and PDGFR&beta;, plays an important role in the proliferation of neural stem cells

Direct interaction of receptor tyrosine kinases, EphA4 and PDGFR&beta;, plays an important role in the proliferation of neural stem cells

The role of cell based therapy in the treatment of Parkinson’s disease

Induced pluripotent stem cells in rat models of Parkinson's disease: A systematic review and meta‑analysis

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Direct interaction of receptor tyrosine kinases, EphA4 and PDGFRβ, plays an important role in the proliferation of neural stem cells

Direct interaction of receptor tyrosine kinases, EphA4 and PDGFRβ, plays an important role in the proliferation of neural stem cells