Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease

Poorya Hosseini; Sabia Z. Abidi; E. Du; Dimitrios P. Papageorgiou; Youngwoon Choi; Yongkeun Park; John M. Higgins; Gregory J. Kato; Subra Suresh; Ming Dao; Zahid Yaqoob; Peter T.C. So

doi:10.1073/pnas.1610435113

Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease

Poorya Hosseini, Sabia Z. Abidi, E. Du, Dimitrios P. Papageorgiou, Youngwoon Choi, Yongkeun Park, John M. Higgins, Gregory J. Kato, Subra Suresh, Ming Dao, Zahid Yaqoob, Peter T.C. So

Research output: Contribution to journal › Article › peer-review

36 Citations (Scopus)

Abstract

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 and morphological 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.

Original language	English
Pages (from-to)	9527-9532
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	113
Issue number	34
DOIs	https://doi.org/10.1073/pnas.1610435113
Publication status	Published - 2016 Aug 23

Bibliographical note

Funding Information:
This research was supported by National Institutes of Health Grants 1R01HL121386-01A1, 9P41EB015871-26A1, 5R01NS051320, 5U01HL114476, and 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; and Koch Institute for Integrative Cancer Research Bridge Project Initiative.

Publisher Copyright:
© 2016, National Academy of Sciences. All rights reserved.

Keywords

Biomarkers
Cell deformability
Cell volume
Cellular properties
Sickle cell anemia

ASJC Scopus subject areas

General

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10.1073/pnas.1610435113

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Hosseini, P., Abidi, S. Z., Du, E., Papageorgiou, D. P., Choi, Y., Park, Y., Higgins, J. M., Kato, G. J., Suresh, S., Dao, M., Yaqoob, Z., & So, P. T. C. (2016). Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease. Proceedings of the National Academy of Sciences of the United States of America, 113(34), 9527-9532. https://doi.org/10.1073/pnas.1610435113

Hosseini, P, Abidi, SZ, Du, E, Papageorgiou, DP, Choi, Y, Park, Y, Higgins, JM, Kato, GJ, Suresh, S, Dao, M, Yaqoob, Z & So, PTC 2016, 'Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 34, pp. 9527-9532. https://doi.org/10.1073/pnas.1610435113

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abstract = "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 and morphological 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.",

keywords = "Biomarkers, Cell deformability, Cell volume, Cellular properties, Sickle cell anemia",

author = "Poorya Hosseini and Abidi, {Sabia Z.} and E. Du and Papageorgiou, {Dimitrios P.} and Youngwoon Choi and Yongkeun Park and Higgins, {John M.} and Kato, {Gregory J.} and Subra Suresh and Ming Dao and Zahid Yaqoob and So, {Peter T.C.}",

note = "Funding Information: This research was supported by National Institutes of Health Grants 1R01HL121386-01A1, 9P41EB015871-26A1, 5R01NS051320, 5U01HL114476, and 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; and Koch Institute for Integrative Cancer Research Bridge Project Initiative. Publisher Copyright: {\textcopyright} 2016, National Academy of Sciences. All rights reserved.",

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AU - Hosseini, Poorya

AU - Abidi, Sabia Z.

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AU - Papageorgiou, Dimitrios P.

AU - Choi, Youngwoon

AU - Park, Yongkeun

AU - Higgins, John M.

AU - Kato, Gregory J.

AU - Suresh, Subra

AU - Dao, Ming

AU - Yaqoob, Zahid

AU - So, Peter T.C.

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N2 - 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 and morphological 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.

AB - 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 and morphological 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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Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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