Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 34, Pages 9527-9532Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1610435113
Keywords
sickle cell anemia; biomarkers; cell volume; cell deformability; cellular properties
Categories
Funding
- National Institutes of Health [1R01HL121386-01A1, 9P41EB015871-26A1, 5R01NS051320, 5U01HL114476, 4R44EB012415]
- National Science Foundation Grant [CBET-0939511]
- Hamamatsu Corporation
- Singapore-Massachusetts Institute of Technology Alliance for Research and Technology (SMART) Center, BioSystems and Micromechanics (BioSyM) and Infectious Diseases (ID)
- MIT SkolTech Initiative
- Koch Institute for Integrative Cancer Research Bridge Project Initiative
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Hydroxyurea (HU) has been used clinically to reduce the frequency of painful crisis and the need for blood transfusion in sickle cell disease (SCD) patients. However, the mechanisms underlying such beneficial effects of HU treatment are still not fully understood. Studies have indicated a weak correlation between clinical outcome and molecular markers, and the scientific quest to develop companion biophysical markers have mostly targeted studies of blood properties under hypoxia. Using a common-path interferometric technique, we measure biomechanical andmorphological properties of individual red blood cells in SCD patients as a function of cell density, and investigate the correlation of these biophysical properties with drug intake as well as other clinically measured parameters. Our results show that patient-specific HU effects on the cellular biophysical properties are detectable at normoxia, and that these properties are strongly correlated with the clinically measured mean cellular volume rather than fetal hemoglobin level.
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