Intravenous transplantation of amnion-derived mesenchymal stem cells promotes functional recovery and alleviates intestinal dysfunction after spinal cord injury.
Intravenous transplantation of amnion-derived mesenchymal stem cells promotes functional recovery and alleviates intestinal dysfunction after spinal cord injury.
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DOI：
10.1371/journal.pone.0270606
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
脊髓损伤（Spinal cord injury，SCI）常伴随着由于脊髓自主神经系统的断开而引起的胃肠功能障碍。据报道，胃肠道功能障碍上调肠道通透性，导致肠道微生物组的细菌移位到体循环，这进一步激活全身炎症，加剧神经元损伤。据报道，间充质干细胞（MSC）可改善SCI。在这里，我们的目的是研究他们对相关的胃肠道功能障碍的影响。在大鼠胸中部脊髓损伤模型后一天，静脉内移植人骨髓间充质干细胞（AMSC）。移植细胞的生物分布，行为学评估，脊髓和肠的组织学评估，以阐明AMSC的治疗效果。通过原位杂交和肝脏细菌培养检查肠道微生物组的细菌移位。通过血液细胞因子、脊髓中浸润的免疫细胞和外周免疫组织的大小来检查全身炎症。移植后AMSCs释放多种神经营养因子，主要分布于肝、肺。AMSC移植的动物表现出较小的脊髓损伤和更好的神经功能恢复与保留的神经束。AMSC移植在形态和功能上改善了肠道功能障碍，这阻止了肠道微生物组向体循环的移位。在慢性期接受AMSC的动物中，全身炎症减少。在SCI急性期静脉注射AMSC可以挽救脊髓损伤和肠道功能障碍。减少细菌移位可能有助于减少全身炎症。
Spinal cord injury (SCI) is often accompanied by gastrointestinal dysfunction due to the disconnection of the spinal autonomic nervous system. Gastrointestinal dysfunction reportedly upregulates intestinal permeability, leading to bacterial translocation of the gut microbiome to the systemic circulation, which further activates systemic inflammation, exacerbating neuronal damage. Mesenchymal stem cells (MSC) reportedly ameliorate SCI. Here, we aimed to investigate their effect on the associated gastrointestinal dysfunction. Human amnion-derived MSC (AMSCs) were intravenously transplanted one day after a rat model of midthoracic SCI. Biodistribution of transplanted cells, behavioral assessment, and histological evaluations of the spinal cord and intestine were conducted to elucidate the therapeutic effect of AMSCs. Bacterial translocation of the gut microbiome was examined by in situ hybridization and bacterial culture of the liver. Systemic inflammations were examined by blood cytokines, infiltrating immune cells in the spinal cord, and the size of the peripheral immune tissue. AMSCs released various neurotrophic factors and were mainly distributed in the liver and lung after transplantation. AMSC-transplanted animals showed smaller spinal damage and better neurological recovery with preserved neuronal tract. AMSCs transplantation ameliorated intestinal dysfunction both morphologically and functionally, which prevented translocation of the gut microbiome to the systemic circulation. Systemic inflammations were decreased in animals receiving AMSCs in the chronic phase. Intravenous AMSC administration during the acute phase of SCI rescues both spinal damage and intestinal dysfunction. Reducing bacterial translocation may contribute to decreasing systemic inflammation.
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