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

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

doi:10.1016/j.scr.2021.102642

Cited by 7 publications

(5 citation statements)

References 45 publications

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“…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.…”

Section: Discussionmentioning

confidence: 85%

“…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.…”

Section: Resultsmentioning

confidence: 99%

“…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.…”

Section: Resultsmentioning

confidence: 99%

“…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.…”

Section: Supplementary Figure 2 the Quality Of Grafts Is Dependent On...mentioning

confidence: 99%

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Anin vivoplatform for rebuilding functional neocortical tissue

Quezada

Ward

Bader

et al. 2022

Preprint

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Recent progress in cortical stem cell transplantation has demonstrated its potential to repair the brain. However, current transplant models have yet to demonstrate that the circuitry of transplant-derived neurons can encode useful function to the host. This is likely due to missing cell types within the grafts, abnormal proportions of cell types, abnormal cytoarchitecture, and inefficient vascularization. Here, we devised a transplant platform for testing neocortical tissue prototypes. Dissociated mouse embryonic telencephalic cells in a liquid scaffold were transplanted into aspiration-lesioned adult mouse cortices. The donor neuronal precursors differentiated into upper and deep layer neurons that exhibited synaptic puncta, projected outside of the graft to appropriate brain areas, became electrophysiologically active within one month post-transplant, and responded to visual stimuli. Interneurons and oligodendrocytes were present at normal densities in grafts. Grafts became fully vascularized by 1-week post-transplant and vessels in grafts were perfused with blood. With this paradigm, we could also organize cells into layers. Overall, we have provided proof of concept for an in vivo platform that can be used for developing and testing neocortical-like tissue prototypes.

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Section: Discussionmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Supplementary Figure 2 the Quality Of Grafts Is Dependent On...mentioning

confidence: 99%

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Anin vivoplatform for rebuilding functional neocortical tissue

Quezada

Ward

Bader

et al. 2022

Preprint

Self Cite

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show abstract

“…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.…”

Section: Progressive Brain Replacement: Proposed Techniquementioning

confidence: 99%