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

Anin vivoplatform for rebuilding functional neocortical tissue

“…Despite the presence of vascular endothelial cells in our donor cell population and their importance in contributing new functional blood vessels after transplantation at the site of ischemic strokes (Krzyspiak et al, 2022), the vessels observed here after transplantation to the sites of aspiration lesions are primarily host-derived. Nevertheless, we show that the vessels in these grafts have circulating RBCs and are therefore likely transporting oxygen and nutrients to the new tissue to promote survival and integration.…”

“…1N-0), albeit at a lower density than contralateral cortex (graft 40.8 cells/mm 2 N = 3, contralateral cortex 91.1/mm 2 , p = 0.21). Microglia migrate into the mouse cortex from E9.5 until E14.5, and are therefore present in our donor cell mix (Krzyspiak et al, 2022). However, because microglia do not express Foxg1 and are thus not labeled with GFP, microglia in the graft could be donor- or host-derived.…”

“…Vascular endothelial cells are present in mouse telencephalon at E12.5 and therefore present in the donor cell population (Krzyspiak et al, 2022) To determine the source of donor versus host vessels, we transplanted donor cells from Mesp1 cre/+ ;Rosa26 loxSTOPlox-tdTomato/+ embryos to visualize the donor vessel contribution. At 4 wpt, there were very few donor vessels found in the graft.…”

“…Microglia migrate into the mouse cortex from E9.5 until E14.5, and are therefore present in our donor cell mix (Krzyspiak et al, 2022). However, because microglia do not express Foxg1 and are thus not labeled with GFP, microglia in the graft could be donor-or host-derived.…”

Could an old brain be made young again?

“…Output measures of graft performance are those routinely used by laboratories, including ours. [ 5 - 8 , 10 , 11 , 13 , 15 , 16 ] These include measuring cell survival and cytoarchitecture, mapping of axonal and dendritic connections to and from the graft, and initial functional measures such as recording responses to sensory input and determining the appropriateness of these responses for the location of the graft (e.g., response to visual but not auditory stimuli when the graft is in the visual cortex). Most of these preclinical tests can be performed using adult immune-compromised mice as the hosts for human or primate fetal tissue grafts, although due to the size limitations of the mouse brain, some testing may require larger preclinical models.…”