Intrastriatal transplantation of stem cells from human exfoliated deciduous teeth reduces motor defects in Parkinsonian rats
Intrastriatal transplantation of stem cells from human exfoliated deciduous teeth reduces motor defects in Parkinsonian rats
复制标题
人类脱落乳牙干细胞的纹状体移植可减少帕金森病大鼠的运动缺陷。
DOI：
10.1016/j.jcyt.2018.02.371
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发表时间：
2018-05-01
期刊：
影响因子：
4.5
通讯作者：
Han, Fabin
中科院分区：
文献类型：
--
作者：
Zhang, Nan;Lu, Xianjie;Han, Fabin
背景本研究探讨了人乳牙脱落干细胞（SHED）在帕金森病（PD）大鼠模型中的神经分化和治疗作用。方法.从新鲜牙髓中分离SHED，并通过用Noggin抑制类似母体抗dpp（SMAD）信号传导以及用CHIR 99021、Sonic Hedgehog（SHH）和FGF 8在体外增加来自SHED的多巴胺神经元的转化来诱导SHED分化为神经元和多巴胺神经元。将神经致敏的SHED移植到6-羟基多巴胺（6-OHDA）诱导的PD大鼠纹状体内，以评价其在体神经分化和功能。结果通过新开发的方法，这些SHED被有效地分化为神经元（62.7%）和多巴胺神经元（42.3%）。移植后，神经诱导的SHED显著改善了PD大鼠运动缺陷的恢复。移植的SHED分化为神经元（61%），包括多巴胺神经元（22.3%），并通过形成突触连接整合到宿主大鼠脑中。膜片钳分析显示，移植自SHED的神经元具有与多巴胺神经元相同的膜电位曲线，表明这些细胞是多巴胺神经元样细胞。SHED移植缓解大鼠运动障碍的潜在分子机制可能是通过神经元替代和免疫调节介导的，因为我们检测到移植的多巴胺神经元和从SHED释放的免疫细胞因子。结论使用神经致敏的SHED治疗PD在6-OHDA诱导的大鼠中显示出显著的运动缺陷改善。这些观察结果提供了进一步的证据，SHED可用于PD的基于细胞的治疗。
Background. This study explored the neural differentiation and therapeutic effects of stem cells from human exfoliated deciduous teeth (SHED) in a rat model of Parkinson's disease (PD). Methods. The SHED were isolated from fresh dental pulp and were induced to differentiate to neurons and dopamine neurons by inhibiting similar mothers against dpp (SMAD) signaling with Noggin and increase conversion of dopamine neurons from SHED with CHIR99021, Sonic Hedgehog (SHH) and FGF8 in vitro. The neural-primed SHED were transplanted to the striatum of 6-hydroxydopamine (6-OHDA)-induced PD rats to evaluate their neural differentiation and functions in vivo. Results. These SHED were efficiently differentiated to neurons (62.7%) and dopamine neurons (42.3%) through a newly developed method. After transplantation, the neural-induced SHED significantly improved recovery of the motor deficits of the PD rats. The grafted SHED were differentiated into neurons (61%), including dopamine neurons (22.3%), and integrated into the host rat brain by forming synaptic connections. Patch clamp analysis showed that neurons derived from grafted SHED have the same membrane potential profile as dopamine neurons, indicating these cells are dopamine neuron-like cells. The potential molecular mechanism of SHED transplantation in alleviating motor deficits of the rats is likely to be mediated by neuronal replacement and immune-modulation as we detected the transplanted dopamine neurons and released immune cytokines from SHED. Conclusion. Using neural-primed SHED to treat PD showed significant restorations of motor deficits in 6-OHDA-induced rats. These observations provide further evidence that SHED can be used for cell-based therapy of PD.