Donor-derived vasculature is required to support neocortical cell grafts after stroke

Joanna Krzyspiak, Jingqi Yan, Hiyaa S. Ghosh, Basia Galinski, Pablo J. Lituma, Karina Alvina, Alexandra Quezada, Samantha Kee, Marta Grońska-Pęski, Yi De Tai, Kelsey McDermott, J. Tiago Gonçalves, R. Suzanne Zukin, Daniel A. Weiser, Pablo E. Castillo, Kamran Khodakhah, Jean M. Hébert

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Neural precursor cells (NPCs) transplanted into the adult neocortex generate neurons that synaptically integrate with host neurons, supporting the possibility of achieving functional tissue repair. However, poor survival and functional neuronal recovery of transplanted NPCs greatly limits engraftment. Here, we test the hypothesis that combining blood vessel-forming vascular cells with neuronal precursors improves engraftment. By transplanting mixed embryonic neocortical cells into adult mice with neocortical strokes, we show that transplant-derived neurons synapse with appropriate targets while donor vascular cells form vessels that fuse with the host vasculature to perfuse blood within the graft. Although all grafts became vascularized, larger grafts had greater contributions of donor-derived vessels that increased as a function of their distance from the host-graft border. Moreover, excluding vascular cells from the donor cell population strictly limited graft size. Thus, inclusion of vessel-forming vascular cells with NPCs is required for more efficient engraftment and ultimately for tissue repair.

Original languageEnglish (US)
Article number102642
JournalStem Cell Research
Volume59
DOIs
StatePublished - Mar 2022

Keywords

  • Blood vessels
  • Ischemia
  • Neocortex
  • Transplantation
  • Vascular endothelial cells

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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