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Functional restoration of ex vivo model of pylorus: Co-injection of neural progenitor cells and interstitial cells of Cajal.
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2020-03-17 , DOI: 10.1002/sctm.19-0316 Prabhash Dadhich 1, 2 , Khalil N Bitar 1, 2, 3, 4
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2020-03-17 , DOI: 10.1002/sctm.19-0316 Prabhash Dadhich 1, 2 , Khalil N Bitar 1, 2, 3, 4
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Transplantation of neural stem cells is a promising approach in treatment of intestinal dysfunctionality. The interstitial cells of Cajal (ICCs) are also critical in conditions such as pyloric dysfunctionality and gastroparesis. The objective of this study was to replenish neurons and ICCs in a dysfunctional pylorus as cell‐based therapy to restore functionality. ICCs and enteric neural progenitor cells (NPCs) were isolated from rat duodenum and transduced with fluorescent proteins. Rat pylorus was harvested, and an ex‐vivo neuromuscular dysfunctional model was developed by selective ablation of neurons and ICCs via chemical treatments. Cellular repopulation and restoration of motility were assessed by immunohistochemistry, qPCR, and functional analysis after delivery of fluorescently tagged cells. Chemical treatment of pylorus resulted in significant depletion of ICCs (67%, P = .0024; n = 3) and neural cells (83%, P = .0012; n = 3). Delivered ICCs and NPCs survived and integrated with host muscle layers. Co‐injection of ICCs with NPCs exhibited 34.4% (P = .0004; n = 3) and 61.0% (P = .0003; n = 3) upregulation of ANO1 and βIII tubulin, respectively. This regeneration resulted in the restoration of agonist‐induced excitatory contraction (82%) and neuron evoked relaxation (83%). The functional studies with specific neuronal nitric oxide (NO) synthase blocker confirmed that restoration of relaxation was NO mediated and neuronally derived. The simultaneous delivery of ICCs observed 35.7% higher neuronal differentiation and functional restoration compared with injection of NPCs alone. Injected NPCs and ICCs integrated into the dysfunctional ex vivo pylorus tissues and restored neuromuscular functionality. The co‐transplantation of NPCs and ICCs can be used to treat neurodegenerative disorders of the pylorus.
中文翻译：
幽门离体模型的功能恢复：神经祖细胞和卡哈尔间质细胞的共注射。
神经干细胞移植是治疗肠道功能障碍的一种有前途的方法。 Cajal 间质细胞 (ICC) 在幽门功能障碍和胃轻瘫等疾病中也至关重要。本研究的目的是补充功能失调的幽门中的神经元和 ICC，作为恢复功能的细胞疗法。从大鼠十二指肠中分离 ICC 和肠神经祖细胞 (NPC)，并用荧光蛋白转导。收获大鼠幽门，并通过化学处理选择性消融神经元和 ICC，建立离体神经肌肉功能障碍模型。递送荧光标记细胞后，通过免疫组织化学、qPCR 和功能分析评估细胞增殖和运动恢复。幽门化学处理导致 ICC（67%， P = .0024；n = 3）和神经细胞（83%， P = .0012；n = 3）显着减少。交付的 ICC 和 NPC 存活下来并与宿主肌肉层整合。 ICC 与 NPC 共注射显示 ANO1 和 βIII 微管蛋白分别上调 34.4% ( P = .0004; n = 3) 和 61.0% ( P = .0003; n = 3)。这种再生导致激动剂诱导的兴奋性收缩（82%）和神经元诱发的松弛（83%）的恢复。特定神经元一氧化氮 (NO) 合酶阻滞剂的功能研究证实，放松的恢复是 NO 介导的且源自神经元。与单独注射 NPC 相比，同时注射 ICC 的神经元分化和功能恢复提高了 35.7%。注射的 NPC 和 ICC 整合到功能失调的离体幽门组织中并恢复神经肌肉功能。 NPC 和 ICC 联合移植可用于治疗幽门神经退行性疾病。
更新日期：2020-03-17
中文翻译：
幽门离体模型的功能恢复：神经祖细胞和卡哈尔间质细胞的共注射。
神经干细胞移植是治疗肠道功能障碍的一种有前途的方法。 Cajal 间质细胞 (ICC) 在幽门功能障碍和胃轻瘫等疾病中也至关重要。本研究的目的是补充功能失调的幽门中的神经元和 ICC，作为恢复功能的细胞疗法。从大鼠十二指肠中分离 ICC 和肠神经祖细胞 (NPC)，并用荧光蛋白转导。收获大鼠幽门，并通过化学处理选择性消融神经元和 ICC，建立离体神经肌肉功能障碍模型。递送荧光标记细胞后，通过免疫组织化学、qPCR 和功能分析评估细胞增殖和运动恢复。幽门化学处理导致 ICC（67%， P = .0024；n = 3）和神经细胞（83%， P = .0012；n = 3）显着减少。交付的 ICC 和 NPC 存活下来并与宿主肌肉层整合。 ICC 与 NPC 共注射显示 ANO1 和 βIII 微管蛋白分别上调 34.4% ( P = .0004; n = 3) 和 61.0% ( P = .0003; n = 3)。这种再生导致激动剂诱导的兴奋性收缩（82%）和神经元诱发的松弛（83%）的恢复。特定神经元一氧化氮 (NO) 合酶阻滞剂的功能研究证实，放松的恢复是 NO 介导的且源自神经元。与单独注射 NPC 相比，同时注射 ICC 的神经元分化和功能恢复提高了 35.7%。注射的 NPC 和 ICC 整合到功能失调的离体幽门组织中并恢复神经肌肉功能。 NPC 和 ICC 联合移植可用于治疗幽门神经退行性疾病。
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