The Institute for Tissue Engineering and Regenerative Medicine, Liaocheng University/Liaocheng People's Hospital, Liaocheng, Shandong, China.
Department of Neurology, Liaocheng People's Hospital, Liaocheng, Shandong, China.
Cytotherapy. 2018 May;20(5):670-686. doi: 10.1016/j.jcyt.2018.02.371. Epub 2018 Mar 22.
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).
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.
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.
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.
本研究探讨了人乳牙干细胞（SHED）在帕金森病（PD）大鼠模型中的神经分化和治疗作用。
从新鲜牙髓中分离出 SHED，通过 Noggin 抑制相似母体对抗 dpp（SMAD）信号，体外诱导其向神经元和多巴胺神经元分化，用 CHIR99021、 Sonic Hedgehog（SHH）和 FGF8 增加多巴胺神经元从 SHED 的转化率。将神经诱导的 SHED 移植到 6-羟多巴胺（6-OHDA）诱导的 PD 大鼠纹状体中，评估其体内的神经分化和功能。
通过新开发的方法，这些 SHED 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 大鼠运动功能障碍的恢复。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大脑中。膜片钳分析表明，源自移植 SHED 的神经元具有与多巴胺神经元相同的膜电位特征，表明这些细胞是多巴胺神经元样细胞。SHED 移植缓解大鼠运动功能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 SHED 释放的免疫细胞因子。
使用神经诱导的 SHED 治疗 PD 可显著恢复 6-OHDA 诱导的大鼠运动功能障碍。这些观察结果进一步证明了 SHED 可用于 PD 的细胞治疗。
