The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, United States of America; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, United States of America.
The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, United States of America; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, United States of America.
Exp Neurol. 2020 Jul;329:113316. doi: 10.1016/j.expneurol.2020.113316. Epub 2020 Apr 15.
The development and translation of cell therapies have been hindered by an inability to predict and evaluate their efficacy after transplantation. Using an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis (MS), we studied attenuation of the diffuse injury characteristic of EAE and MS by transplanted glial-restricted precursor cells (GRPs). We assessed the potential of on-resonance variable delay multiple pulse (onVDMP) chemical exchange saturation transfer (CEST) MRI to visualize this attenuation. Allogeneic GRPs transplanted in the motor cortex or lateral ventricles attenuated paralysis in EAE mice and attenuated differences compared to naïve mice in onVDMP CEST signal 5 days after transplantation near the transplantation site. Histological analysis revealed that transplanted GRPs co-localized with attenuated astrogliosis. Hence, diffuse injury-sensitive onVDMP CEST MRI may complement conventional MRI to locate and monitor tissue regions responsive to GRP therapy.
细胞疗法的发展和转化受到阻碍,因为无法预测和评估其移植后的疗效。我们使用多发性硬化症(MS)的实验性自身免疫性脑脊髓炎(EAE)小鼠模型,研究了胶质限制定向前体细胞(GRP)移植对 EAE 和 MS 的弥漫性损伤的抑制作用。我们评估了共振变量延迟多脉冲(onVDMP)化学交换饱和转移(CEST)MRI 来可视化这种衰减的潜力。在运动皮层或侧脑室中移植同种异体 GRP 可减轻 EAE 小鼠的瘫痪,并在移植后 5 天在移植部位附近,与未受感染的小鼠相比,减轻了 onVDMP CEST 信号的差异。组织学分析显示,移植的 GRP 与减弱的星形胶质细胞增生共定位。因此,弥散性损伤敏感的 onVDMP CEST MRI 可与常规 MRI 互补,以定位和监测对 GRP 治疗有反应的组织区域。