Bone marrow transplant protects mice from sickle cell-mediated large artery remodeling

Sickle cell disease (SCD) is a hereditary blood disorder that causes sickling of red blood cells under deoxygenation, which stiffens and damages the cells. Individuals homozygous for the mutant β-globin S allele (SS) endure complications including progressive arterial damage and heightened risk of stroke. The effectiveness of bone marrow transplantation (BMT), now the only curative treatment for SCD, in halting or reversing SCD-mediated arteriopathy remains unclear. This study used two distinct conditioning regimens, x-ray irradiation and chemotherapy, in a Townes humanized murine model of SCD. Mice homozygous for the SS allele underwent BMT at 2 or 4 months of age, time points that we deemed early or late, respectively. Label-free magnetic resonance angiography (MRA) was performed to longitudinally monitor common carotid artery luminal areas in living mice pre- and repeatedly post-BMT, followed by histological analysis of the arteries at euthanasia. Myeloablative chemotherapy demonstrated higher survivability in SS mice compared with x-ray irradiation. SS mice exhibited arterial outward expansion by 3 months and thinning of the medial layer at 5 months, which are characteristics of a weakened arterial wall. BMT at 2 months effectively halted this expansion, maintaining smaller luminal areas in SS mice. However, BMT at 4 months did not reverse arteriopathy, indicating the importance of early intervention. This work emphasizes how MRA can be used as a noninvasive method for assessing arteriopathy progression and demonstrates that the timing of BMT is crucial in mitigating sickle cell-induced large artery remodeling.