Stem Cell Reviews and Reports ( IF 4.5 ) Pub Date : 2021-08-28 , DOI: 10.1007/s12015-021-10223-w Hideaki Matsumura 1, 2, 3 , Aiki Marushima 1, 3 , Hiroshi Ishikawa 1, 3 , Junko Toyomura 1, 3 , Akihiro Ohyama 1, 3 , Miho Watanabe 1, 3, 4 , Shohei Takaoka 2, 3, 5 , Hiroki Bukawa 5 , Akira Matsumura 1 , Yuji Matsumaru 1, 3 , Eiichi Ishikawa 1
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Abstract
Human mesenchymal stem cells are a promising cell source for the treatment of stroke. Their primary mechanism of action occurs via neuroprotective effects by trophic factors, anti-inflammatory effects, and immunomodulation. However, the regeneration of damaged neuronal networks by cell transplantation remains challenging. We hypothesized that cells induced to neural lineages would fit the niche, replace the lesion, and be more effective in improving symptoms compared with stem cells themselves. We investigated the characteristics of induced neural cells from human dental pulp tissue and compared the transplantation effects between these induced neural cells and uninduced dental pulp stem cells. Induced neural cells or dental pulp stem cells were intracerebrally transplanted 5 days after cerebral infarction induced by permanent middle cerebral artery occlusion in immunodeficient mice. Effects on functional recovery were also assessed through behavior testing. We used immunohistochemistry and neuron tracing to analyze the differentiation, axonal extension, and connectivity of transplanted cells to the host’s neural circuit. Transplantation of induced neural cells from human dental pulp ameliorated functional recovery after cerebral infarction compared with dental pulp stem cells. The induced neural cells comprised both neurons and glia and expressed functional voltage, and they were more related to neurogenesis in terms of transcriptomics. Induced neural cells had a higher viability than did dental pulp stem cells in hypoxic culture. We showed that induced neural cells from dental pulp tissue offer a novel therapeutic approach for recovery after cerebral infarction.
Graphic Abstract
中文翻译：
人牙髓中的诱导神经细胞可改善脑梗死小鼠模型的功能恢复
摘要
人间充质干细胞是治疗中风的有前途的细胞来源。它们的主要作用机制是通过营养因子的神经保护作用、抗炎作用和免疫调节作用发生的。然而，通过细胞移植再生受损神经元网络仍然具有挑战性。我们假设，与干细胞本身相比，诱导成神经谱系的细胞将适合生态位，取代病变，并更有效地改善症状。我们研究了来自人牙髓组织的诱导神经细胞的特征，并比较了这些诱导神经细胞和未诱导的牙髓干细胞之间的移植效果。免疫缺陷小鼠永久性大脑中动脉闭塞诱发脑梗死5天后，将诱导的神经细胞或牙髓干细胞进行脑内移植。还通过行为测试评估了对功能恢复的影响。我们使用免疫组织化学和神经元追踪来分析移植细胞与宿主神经回路的分化、轴突延伸和连接性。与牙髓干细胞相比，人牙髓诱导神经细胞移植可改善脑梗塞后的功能恢复。诱导的神经细胞由神经元和神经胶质组成，表达功能电压，在转录组学方面与神经发生更相关。在缺氧培养中，诱导的神经细胞比牙髓干细胞具有更高的活力。
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