Kings College London, Institute of Psychiatry, Department of Neuroscience, London SE5 9NU, UK.
Biomaterials. 2012 Apr;33(10):2858-71. doi: 10.1016/j.biomaterials.2011.12.033. Epub 2012 Jan 13.
Transplantation of human neural stem cells (hNSCs) is emerging as a viable treatment for stroke related brain injury. However, intraparenchymal grafts do not regenerate lost tissue, but rather integrate into the host parenchyma without significantly affecting the lesion cavity. Providing a structural support for the delivered cells appears important for cell based therapeutic approaches. The non-invasive monitoring of therapeutic methods would provide valuable information regarding therapeutic strategies but remains a challenge. Labeling transplanted cells with metal-based (1)H-magnetic resonance imaging (MRI) contrast agents affects the visualization of the lesion cavity. Herein, we demonstrate that a (19)F-MRI contrast agent can adequately monitor the distribution of transplanted cells, whilst allowing an evaluation of the lesion cavity and the formation of new tissue on (1)H-MRI scans. Twenty percent of cells labeled with the (19)F agent were of host origin, potentially reflecting the re-uptake of label from dead transplanted cells. Both T(2)- and diffusion-weighted MRI scans indicated that transplantation of hNSCs suspended in a gel form of a xenogeneic extracellular matrix (ECM) bioscaffold resulted in uniformly distributed cells throughout the lesion cavity. However, diffusion MRI indicated that the injected materials did not yet establish diffusion barriers (i.e. cellular network, fiber tracts) normally found within striatal tissue. The ECM bioscaffold therefore provides an important support to hNSCs for the creation of de novo tissue and multi-nuclei MRI represents an adept method for the visualization of some aspects of this process. However, significant developments of both the transplantation paradigm, as well as regenerative imaging, are required to successfully create new tissue in the lesion cavity and to monitor this process non-invasively.
人神经干细胞（hNSCs）移植作为一种治疗中风相关脑损伤的可行方法正在兴起。然而，脑实质内移植并不能再生丢失的组织，而是整合到宿主实质中，而不会显著影响病变腔。为递送到的细胞提供结构支持对于基于细胞的治疗方法似乎很重要。治疗方法的非侵入性监测将为治疗策略提供有价值的信息，但仍然是一个挑战。用基于金属的（1）H 磁共振成像（MRI）对比剂标记移植细胞会影响病变腔的可视化。在此，我们证明（19）F-MRI 对比剂可以充分监测移植细胞的分布，同时允许在（1）H-MRI 扫描上评估病变腔和新组织的形成。用（19）F 标记的 20%的细胞为宿主来源，可能反映了从死亡的移植细胞中重新摄取标记物。T（2）和扩散加权 MRI 扫描均表明，悬浮在异种细胞外基质（ECM）生物支架凝胶形式中的 hNSCs 移植导致细胞均匀分布在病变腔内。然而，扩散 MRI 表明，注射的材料尚未建立扩散屏障（即细胞网络、纤维束），这些屏障通常存在于纹状体组织中。因此，ECM 生物支架为 hNSCs 提供了新组织形成的重要支持，多核 MRI 是可视化该过程某些方面的一种有效方法。然而，需要对移植范式以及再生成像进行重大改进，以便成功地在病变腔内产生新组织并进行非侵入性监测这个过程。
