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磁共振成像在啮齿动物和灵长类动物脑内人类神经干细胞的应用。

Magnetic resonance imaging of human neural stem cells in rodent and primate brain.

机构信息

Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.

Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA.

出版信息

Stem Cells Transl Med. 2021 Jan;10(1):83-97. doi: 10.1002/sctm.20-0126. Epub 2020 Aug 25.

Abstract

Stem cell transplantation therapies are currently under investigation for central nervous system disorders. Although preclinical models show benefit, clinical translation is somewhat limited by the absence of reliable noninvasive methods to confirm targeting and monitor transplanted cells in vivo. Here, we assess a novel magnetic resonance imaging (MRI) contrast agent derived from magnetotactic bacteria, magneto-endosymbionts (MEs), as a translatable methodology for in vivo tracking of stem cells after intracranial transplantation. We show that ME labeling provides robust MRI contrast without impairment of cell viability or other important therapeutic features. Labeled cells were visualized immediately post-transplantation and over time by serial MRI in nonhuman primate and mouse brain. Postmortem tissue analysis confirmed on-target grft location, and linear correlations were observed between MRI signal, cell engraftment, and tissue ME levels, suggesting that MEs may be useful for determining graft survival or rejection. Overall, these findings indicate that MEs are an effective tool for in vivo tracking and monitoring of cell transplantation therapies with potential relevance to many cellular therapy applications.

摘要

干细胞移植疗法目前正在针对中枢神经系统疾病进行研究。虽然临床前模型显示出了益处,但由于缺乏可靠的非侵入性方法来确认靶向性并在体内监测移植细胞,临床转化受到了一定限制。在这里,我们评估了一种源自趋磁细菌的新型磁共振成像 (MRI) 造影剂,即磁内共生体 (MEs),作为一种可转化的方法,用于在颅内移植后对干细胞进行体内追踪。我们发现,ME 标记提供了强大的 MRI 对比,而不会损害细胞活力或其他重要的治疗特征。在非人类灵长类动物和小鼠脑中,通过连续 MRI 可以立即在移植后以及随着时间的推移观察到标记细胞。死后组织分析证实了靶移植部位,并且 MRI 信号、细胞植入和组织 ME 水平之间存在线性相关性,这表明 ME 可能有助于确定移植物的存活或排斥。总体而言,这些发现表明 ME 是一种用于细胞移植疗法体内追踪和监测的有效工具,可能与许多细胞治疗应用相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b869/7780819/1e1ba2cf05b7/SCT3-10-83-g001.jpg

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