Differential effect on the growth plate of gene therapy and HCT. (A) Representative pictures of the proximal epiphysis of the tibiae from mock-transplanted and treated mice (hematoxylin and eosin staining), as indicated. The growth plate is disorganized and has an irregular morphology in both mock-transplanted MPS I and HCT mice (the GT mouse shown in panels A-B had a VCN of 6 on bone marrow; the HCT mouse had a donor-cell engraftment of 80% on PBMCs). Magnifications, ×5 and ×20. (B-C) The ratio between the perimeter and the length of the growth plate (B) was calculated, and the number of chondrocytes aligned in columns perpendicular to the major axis of the growth plate (C) was counted (see supplemental Figure 2 for detailed explanation) for 5 representative MPS I, HCT, GT, and WT mice (≥ 3 representative sections per mouse). Mean and min/max values are shown: *P < .05; **P < .01; ***P < .001 with 1-way ANOVA.