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

IF 15.8 1区 医学 Q1 CELL BIOLOGY Science Translational Medicine Pub Date : 2025-02-26
Liana Hatoum, Hannah Song, David Alexander, Victor O. Omojola, Hannah Moore, Julia N. Frank, Edward A. Botchwey, Manu O. Platt
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Abstract

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.
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来源期刊
Science Translational Medicine
Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
26.70
自引率
1.20%
发文量
309
审稿时长
1.7 months
期刊介绍: Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.
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