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人诱导多能干细胞支持脊髓损伤模型中的功能恢复。

Human induced neural stem cells support functional recovery in spinal cord injury models.

机构信息

Laboratory of Cell Function Regulation, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.

Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.

出版信息

Exp Mol Med. 2023 Jun;55(6):1182-1192. doi: 10.1038/s12276-023-01003-2. Epub 2023 Jun 1.

Abstract

Spinal cord injury (SCI) is a clinical condition that leads to permanent and/or progressive disabilities of sensory, motor, and autonomic functions. Unfortunately, no medical standard of care for SCI exists to reverse the damage. Here, we assessed the effects of induced neural stem cells (iNSCs) directly converted from human urine cells (UCs) in SCI rat models. We successfully generated iNSCs from human UCs, commercial fibroblasts, and patient-derived fibroblasts. These iNSCs expressed various neural stem cell markers and differentiated into diverse neuronal and glial cell types. When transplanted into injured spinal cords, UC-derived iNSCs survived, engrafted, and expressed neuronal and glial markers. Large numbers of axons extended from grafts over long distances, leading to connections between host and graft neurons at 8 weeks post-transplantation with significant improvement of locomotor function. This study suggests that iNSCs have biomedical applications for disease modeling and constitute an alternative transplantation strategy as a personalized cell source for neural regeneration in several spinal cord diseases.

摘要

脊髓损伤(SCI)是一种导致感觉、运动和自主功能永久和/或进行性障碍的临床病症。不幸的是,目前尚无治疗 SCI 的医学标准来逆转损伤。在这里,我们评估了直接从人尿液细胞(UCs)诱导的神经干细胞(iNSCs)在 SCI 大鼠模型中的作用。我们成功地从人 UCs、商业成纤维细胞和患者来源的成纤维细胞中生成 iNSCs。这些 iNSCs 表达各种神经干细胞标志物,并分化为多种神经元和神经胶质细胞类型。当移植到损伤的脊髓中时,UC 衍生的 iNSCs 存活、植入并表达神经元和神经胶质标志物。大量轴突从移植物中延伸出很长的距离,导致移植后 8 周宿主和移植物神经元之间的连接,运动功能有显著改善。这项研究表明,iNSCs 可用于疾病建模的生物医学应用,并构成了一种替代的移植策略,作为几种脊髓疾病中神经再生的个性化细胞来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d34c/10318049/8dae96e0a54d/12276_2023_1003_Fig1_HTML.jpg

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