Fig. 4: Engraftment of Bone-marrow Derived ABCD1 Sufficient Cells into the Brain Vasculature. | Nature Communications

Fig. 4: Engraftment of Bone-marrow Derived ABCD1 Sufficient Cells into the Brain Vasculature.

From: Hematopoietic stem-cell gene therapy is associated with restored white matter microvascular function in cerebral adrenoleukodystrophy

Fig. 4

a Longitudinal mean Kapp and mean VA in distant NAWM (blue), mean Kapp in the lesion (red) and mean perilesional rCTH (orange) following gene therapy (GT, n = 7–15 each time point). Black dots indicate grouped mean, error bars indicate SD. Mixed effects analysis with Geisser-Greenhouse correction, a single pooled variance and P values (vs. PRE) adjusted for multiplicity. b Correlation plot showing post treatment VA in NAWM vs. relative monthly T2w lesion growth V1-1Y (n = 10). Line indicates regression; two-tailed Pearson’s correlation. c Plot showing the relationship of VCN in CD14+ at 30 days and T2W lesion growth over two years (n = 10, simple linear regression). d Longitudinal data on percentage of CD14+ and nucleated cells expressing ALD protein in the peripheral blood after infusion of GT (n = 15). Dotted line connects means; error bars indicate SD. e In vitro Blood outgrowth endothelial cell morphology after GT at day 1, 6 and 37 from a patient with at baseline missing ALDP expressio. Microphotographs of representative confocal imaging show ALDP expression in peroxisomes as demonstrated by colocalization with catalase. Two biological replicates with three technical replicates each were performed. f Ex vivo representative microphotographs of brain specimens from a control (CON), an untreated patient with CALD with no ABCD1 expression, and a patient with CALD treated with allo-HSCT, 15 months after successful bone marrow peripheral blood engraftment. Following allo-HSCT punctate (peroxisomal) high ALDP expression is observed in microvascular pericytes (white arrows) and endothelial cells (white arrowheads) suggesting brain mural vascular engraftment of donor (ABCD1+) cells. Large numbers of infiltrating donor-ALDP expressing perivascular mononuclear cells were found in the perilesional white matter micro vessels after allo-HSCT. Three consecutive sections each were processed with the same technique. Source data are provided as a Source Data file.

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