Abstract
In situ tissue engineering within a stroke cavity is gradually emerging as a novel therapeutic paradigm. Considering the varied lesion topology within each subject, the placement and distribution of cells within the lesion cavity is challenging. The use of multiple cell types to reconstruct damaged tissue illustrates the complexity of the process, but also highlights the challenges to provide a non-invasive assessment. The distribution of implanted cells within the lesion cavity and crucially the contribution of neural stem cells and endothelial cells to morphogenesis could be visualized simultaneously using two paramagnetic chemical exchange saturation transfer (paraCEST) agents. The development of sophisticated imaging methods is essential to guide delivery of the building blocks for in situ tissue engineering, but will also be essential to understand the dynamics of cellular interactions leading to the formation of de novo tissue.
Highlights
Voxel[14], its inherent sensitivity is low and it requires multi-nuclear MRI capabilities, limiting its wider applicability
The emergence of in situ tissue engineering to repair damaged brain tissue requires the development of novel non-invasive imaging techniques that can selectively visualize different cellular fractions[11]
Paramagnetic CEST contrast agents present a unique opportunity to visualize simultaneously multiple populations of cells and to report on their distribution within soft tissue[17]. This approach here allowed us to image in vivo the distribution of human neural stem cells, as well as brain endothelial cells, that were co-implanted into a stroke cavity to form de novo brain tissue
Summary
Voxel[14], its inherent sensitivity is low and it requires multi-nuclear MRI capabilities, limiting its wider applicability. Paramagnetic chemical exchange saturation transfer (paraCEST) affords a selective visualization of independent paraCEST agents with better sensitivity[15,16]. ParaCEST agents, Eu- and Yb-HPDO3A have been used to pre-label macrophages and tumor cells for proof-of-principle simultaneous in vivo visualization using MRI17,18. We here report the use of Eu- and Yb-HPDO3A to visualize simultaneously and non-invasively neural stem cells and endothelial cells after implantation into the stroke cavity
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