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Boundary cap neural crest stem cells promote angiogenesis after transplantation to avulsed dorsal roots in mice and induce migration of endothelial cells in 3D printed scaffolds.

  • Trolle, Carl1
  • Han, Yilin2
  • Mutt, Shivaprakash Jagalur3
  • Christoffersson, Gustaf3
  • Kozlova, Elena N4
  • 1 Department of Medical Sciences, Uppsala University Hospital, Rehabilitation Medicine, 751 85 Uppsala, Sweden. , (Sweden)
  • 2 Department of Immunology, Genetics and Pathology, Uppsala University Biomedical Center, PO Box 815, 751 08 Uppsala, Sweden. , (Sweden)
  • 3 Department of Medical Cell Biology, Science for Life Laboratory, Uppsala University, PO Box 571, 751 23 Uppsala, Sweden. , (Sweden)
  • 4 Department of Immunology, Genetics and Pathology, Uppsala University Biomedical Center, PO Box 815, 751 08 Uppsala, Sweden. Electronic address: [email protected]. , (Sweden)
Published Article
Neuroscience letters
Publication Date
Mar 11, 2024
DOI: 10.1016/j.neulet.2024.137724
PMID: 38467271


Dorsal root avulsion injuries lead to loss of sensation and to reorganization of blood vessels (BVs) in the injured area. The inability of injured sensory axons to re-enter the spinal cord results in permanent loss of sensation, and often also leads to the development of neuropathic pain. Approaches that restore connection between peripheral sensory axons and their CNS targets are thus urgently need. Previous research has shown that sensory axons from peripherally grafted human sensory neurons are able to enter the spinal cord by growing along BVs which penetrate the CNS from the spinal cord surface. In this study we analysed the distribution of BVs after avulsion injury and how their pattern is affected by implantation at the injury site of boundary cap neural crest stem cells (bNCSCs), a transient cluster of cells, which are located at the boundary between the spinal cord and peripheral nervous system and assist the growth of sensory axons from periphery into the spinal cord during development. The superficial dorsal spinal cord vasculature was examined using intravital microscopy and intravascular BV labelling. bNCSC transplantation increased vascular volume in a non-dose responsive manner, whereas dorsal root avulsion alone did not decrease the vascular volume. To determine whether bNCSC are endowed with angiogenic properties we prepared 3D printed scaffolds, containing bNCSCs together with rings prepared from mouse aorta. We show that bNCSC do induce migration and assembly of endothelial cells in this system. These findings suggest that bNCSC transplant can promote vascularization in vivo and contribute to BV formation in 3D printed scaffolds. Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.

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