Perfluorocarbon Labeling of Human Glial-Restricted Progenitors for 19 F Magnetic Resonance Imaging.
Perfluorocarbon Labeling of Human Glial-Restricted Progenitors for 19 F Magnetic Resonance Imaging.
复制标题
用于 19 F 磁共振成像的人类神经胶质限制祖细胞的全氟化碳标记。
DOI：
10.1002/sctm.18-0094
复制
发表时间：
2019
影响因子：
6
通讯作者：
Maragakis,NicholasJ
中科院分区：
文献类型：
--
作者：
Richard,Jean-Philippe;Hussain,Uzma;Gross,Sarah;Taga,Arens;Kouser,Mehreen;Almad,Akshata;Campanelli,JamesT;Bulte,JeffWM;Maragakis,NicholasJ
评估中枢神经系统(CNS)干细胞移植潜在疗效的基本限制之一是无创和纵向监测细胞存活和迁移的能力。在肌萎缩侧索硬化症(ALS)模型移植后，人类胶质限制祖细胞(HGRP)细胞(Q细胞)在提供神经保护方面的有效性已被研究，并已获得食品和药物管理局(FDA)的研究新药(IND)用于ALS患者的椎管内移植。此外，这些细胞用于治疗的临床开发将依赖于使用非侵入性成像方法跟踪细胞的能力，以及移植的GRP具有与疾病相关的活动的验证。作为开发的第一步，我们研究了使用全氟碳(PFC)双模式(19F磁共振成像[MRI]和荧光)示踪剂来标记培养和脊髓移植后的Q细胞。全氟化碳有许多潜在的好处，使它们在临床上很受欢迎。它们是定量的、非侵入性的、生物惰性的，并且具有高度的特异性。在这项研究中，我们为Q细胞开发了优化的PFC标记方案，并证明了PFC不会显著改变Q细胞的神经胶质特性。我们还表明，无论是在体外还是在移植到小鼠脊髓腹角后，PFC都不会干扰向星形胶质细胞的分化能力，并且可以通过热点19F磁共振成像在体内观察到。这些研究为在使用19F MRI评估Q细胞移植在未来ALS患者的脑和脊髓中的背景下进一步的临床前发展提供了基础。StemCellsTranslationalMedicine2019；8:355–365Significance声明这项研究证明了将全氟化碳(PFC)掺入人神经胶质细胞限制的祖细胞中用于活体19F磁共振成像的可行性。将PFC用于脑和脊髓疾病(包括ALS)患者的临床移植试验的核心是证明PFC不会显著改变Q细胞产物的胶质细胞特性。最后，无论是在体外还是在移植到小鼠脊髓腹角后，PFC都不会干扰分化为星形胶质细胞的能力，并且可以在移植后使用19F MRI显示大脑中的PFC。这些研究为未来利用大型动物对Q细胞进行19F核磁共振成像研究奠定了基础，并最终用于人类临床试验。
One of the fundamental limitations in assessing potential efficacy in Central Nervous System (CNS) transplantation of stem cells is the capacity for monitoring cell survival and migration noninvasively and longitudinally. Human glial-restricted progenitor (hGRP) cells (Q-Cells) have been investigated for their utility in providing neuroprotection following transplantation into models of amyotrophic lateral sclerosis (ALS) and have been granted a Food and Drug Administration (FDA) Investigational New Drug (IND) for intraspinal transplantation in ALS patients. Furthermore, clinical development of these cells for therapeutic use will rely on the ability to track the cells using noninvasive imaging methodologies as well as the verification that the transplanted GRPs have disease-relevant activity. As a first step in development, we investigated the use of a perfluorocarbon (PFC) dual-modal (19F magnetic resonance imaging [MRI] and fluorescence) tracer agent to label Q-Cells in culture and following spinal cord transplantation. PFCs have a number of potential benefits that make them appealing for clinical use. They are quantitative, noninvasive, biologically inert, and highly specific. In this study, we developed optimized PFC labeling protocols for Q-Cells and demonstrate that PFCs do not significantly alter the glial identity of Q-Cells. We also show that PFCs do not interfere with the capacity for differentiation into astrocytes either in vitro or following transplantation into the ventral horn of the mouse spinal cord, and can be visualized in vivo by hot spot19F MRI. These studies provide a foundation for further preclinical development of PFCs within the context of evaluating Q-Cell transplantation in the brain and spinal cord of future ALS patients using19F MRI. StemCellsTranslationalMedicine2019;8:355–365Significance StatementThis study demonstrates the feasibility of incorporating perfluorocarbon (PFC) into human glial-restricted progenitors for in vivo19F magnetic resonance imaging (MRI). Central to the use of PFC for clinical trials of transplantation into patients with diseases of the brain and spinal cord, including ALS, is the demonstration that PFCs do not significantly alter the glial identity of the Q-Cell product. Finally, PFCs did not interfere with the capacity for differentiation into astrocytes either in vitro or following transplantation into the ventral horn of the mouse spinal cord and can be visualized in the brain using19F MRI following transplantation. These studies form the foundation for future19F MRI imaging studies of Q-Cells using large animal and, eventually, human clinical trials.