Fetal cortical allografts project massively through the adult cortex
Section snippets
Selection of donor tissue and grafting procedure
Grafts were blocks of presumptive occipital cortical areas excised from transgenic E15 mice embryos overexpressing the eGFP under the control of a chicken β-actin promoter [C57BI/6-TgN(β-act-EGFP)Osb strain; a generous gift from Dr. M. Okabe, Osaka University; Okabe et al., 1997]. Under anesthesia (Avertin; 25 μl/g), the blocks were implanted the same day into brain cavities made into the posterior cortex of adult albino mice (18 weeks old; N=9; NMRI strain; R. Janvier, France). The skull over
Results
On skull opening, transplants of presumptive occipital origin were found occupying 2.5–5.0 mm2 of host cortical tissue in both somatosensory (Som; Fig. 1A) and visual (Vis; Fig. 1A) areas. In all cases, (i) aspirative lesions impinged on the white matter (arrowhead; Fig. 1B); and (ii) approximately 0.5–1 mm2 of the graft base contacted the hippocampus (oriens layer) directly (Fig. 1B, C). Close to the graft boundaries, dislocated eGFP-labeled donor astrocytes were clearly evidenced, mainly in
Discussion
The central goal of this study was to examine whether E15–16 occipital tissue allografts placed in the occipital cortex of mature rodents project to normally targeted brain areas. The topography of these efferents has been reviewed extensively (Wiesendanger and Wiesendanger, 1982, Carey and Neal, 1985, Olavarria and Van Sluyters, 1985, Serizawa et al., 1994, Sefton and Dreher, 1995, Zilles and Wree, 1995, McDonald and Mascagni, 1996). Briefly, in addition to reciprocal connections, ipsilateral
Acknowledgements
This work was supported in part by the CNRS and by a grant from the Fondation pour la Recherche Médicale (FDT20020705037/1) awarded to Miss L. Domballe. Thanks to Dr. A. Cantereau for confocal imaging.
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Axonal Extensions along Corticospinal Tracts from Transplanted Human Cerebral Organoids
2020, Stem Cell ReportsCitation Excerpt :We found that 10w-organoids, which are in the CPN-generating stage, have a lower risk of graft overgrowth. In previous studies describing the transplantation of embryonic cerebral cortex, E14–E15 mice, which corresponds to the CPN-generating stage, were used as the grafts (Ballout et al., 2016, 2019; Gaillard et al., 2004, 2007; Peron et al., 2017), which would explain why graft overgrowth did not become a problem in those studies. The observed enhancement of the graft survival and axonal extensions of 10w-organoids by delaying the transplantation 1 week after the cortical resection suggests that adjusting the host brain environment is a possible approach to promoting axonal extensions from cerebral organoids.
Mechanisms and use of neural transplants for brain repair
2017, Progress in Brain ResearchCitation Excerpt :This was further supported by the observation that the growth and extension of the graft-derived GFP-positive fibers were much more restricted in nonlesioned hosts where the intrinsic dopamine projections were left intact. A second example comes from studies performed in Afsaneh Gaillard's Lab using transplants of GFP-expressing cortical tissue, obtained from E14 transgenic mice, and grafted to a cavity made in the sensorimotor cortex of adult wild-type mice (Gaillard et al., 2004, 2007). Again, the results are striking: The graft-derived, GFP-expressing axons could be traced over large distances, within white matter tracts, not only to the contralateral cortex, but also to a number of subcortical targets, including striatum, thalamus, pontine nuclei, and the cervical spinal cord.
Area-specific reestablishment of damaged circuits in the adult cerebral cortex by cortical neurons derived from mouse embryonic stem cells
2015, NeuronCitation Excerpt :However, studies using more sensitive and specific tools to lesion the cortex and to trace the projections of the grafted cells have reported that grafted embryonic cortex neurons could display specific patterns of long-range projections, at least in some conditions (Fricker-Gates et al., 2002; Gaillard et al., 2007; Hernit-Grant and Macklis, 1996). Most strikingly, it was reported that grafted embryonic cortex neurons could effectively reestablish specific patterns of subcortical projections and synapses following cortical lesions (Gaillard et al., 2004, 2007). While these studies open the possibility of cell transplantation for cortical repair, the very limited accessibility of human fetal cortical tissue constitutes a serious limitation to consider such approaches in a clinical setting.
Restoration of damaged cortical pathways by neural grafting
2018, Medecine/SciencesNeuronal replacement therapy: previous achievements and challenges ahead
2017, npj Regenerative Medicine