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Article

Characterization of Hematopoiesis in Sickle Cell Disease by Prospective Isolation of Stem and Progenitor Cells

by
Seda S. Tolu
1,
Kai Wang
2,
Zi Yan
2,
Shouping Zhang
2,
Karl Roberts
2,
Andrew S. Crouch
1,
Gracy Sebastian
1,
Mark Chaitowitz
1,
Eric D. Fornari
3,
Evan M. Schwechter
3,
Joan Uehlinger
4,
Deepa Manwani
5,
Caterina P. Minniti
1 and
Eric E. Bouhassira
1,2,*
1
Department of Medicine, Division of Hematology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
3
Department of Orthopedic Surgery, Montefiore Medical Center, Bronx, NY 10461, USA
4
Department of Pathology, Division of Transfusion Medicine, Montefiore Health System, Bronx, NY 10467, USA
5
Pediatric Hematology/Oncology/Marrow and Blood Cell Transplantation, Montefiore Health System, Bronx, NY 10467, USA
*
Author to whom correspondence should be addressed.
Cells 2020, 9(10), 2159; https://doi.org/10.3390/cells9102159
Submission received: 17 August 2020 / Revised: 15 September 2020 / Accepted: 18 September 2020 / Published: 24 September 2020
(This article belongs to the Section Stem Cells)
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Abstract

The consequences of sickle cell disease (SCD) include ongoing hematopoietic stress, hemolysis, vascular damage, and effect of chronic therapies, such as blood transfusions and hydroxyurea, on hematopoietic stem and progenitor cell (HSPC) have been poorly characterized. We have quantified the frequencies of nine HSPC populations by flow cytometry in the peripheral blood of pediatric and adult patients, stratified by treatment and control cohorts. We observed broad differences between SCD patients and healthy controls. SCD is associated with 10 to 20-fold increase in CD34dim cells, a two to five-fold increase in CD34bright cells, a depletion in Megakaryocyte-Erythroid Progenitors, and an increase in hematopoietic stem cells, when compared to controls. SCD is also associated with abnormal expression of CD235a as well as high levels CD49f antigen expression. These findings were present to varying degrees in all patients with SCD, including those on chronic therapy and those who were therapy naive. HU treatment appeared to normalize many of these parameters. Chronic stress erythropoiesis and inflammation incited by SCD and HU therapy have long been suspected of causing premature aging of the hematopoietic system, and potentially increasing the risk of hematological malignancies. An important finding of this study was that the observed concentration of CD34bright cells and of all the HSPCs decreased logarithmically with time of treatment with HU. This correlation was independent of age and specific to HU treatment. Although the number of circulating HSPCs is influenced by many parameters, our findings suggest that HU treatment may decrease premature aging and hematologic malignancy risk compared to the other therapeutic modalities in SCD.
Keywords: sickle cell disease; hematopoietic stem cells; hydroxyurea; transfusion sickle cell disease; hematopoietic stem cells; hydroxyurea; transfusion
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MDPI and ACS Style

Tolu, S.S.; Wang, K.; Yan, Z.; Zhang, S.; Roberts, K.; Crouch, A.S.; Sebastian, G.; Chaitowitz, M.; Fornari, E.D.; Schwechter, E.M.; et al. Characterization of Hematopoiesis in Sickle Cell Disease by Prospective Isolation of Stem and Progenitor Cells. Cells 2020, 9, 2159. https://doi.org/10.3390/cells9102159

AMA Style

Tolu SS, Wang K, Yan Z, Zhang S, Roberts K, Crouch AS, Sebastian G, Chaitowitz M, Fornari ED, Schwechter EM, et al. Characterization of Hematopoiesis in Sickle Cell Disease by Prospective Isolation of Stem and Progenitor Cells. Cells. 2020; 9(10):2159. https://doi.org/10.3390/cells9102159

Chicago/Turabian Style

Tolu, Seda S., Kai Wang, Zi Yan, Shouping Zhang, Karl Roberts, Andrew S. Crouch, Gracy Sebastian, Mark Chaitowitz, Eric D. Fornari, Evan M. Schwechter, and et al. 2020. "Characterization of Hematopoiesis in Sickle Cell Disease by Prospective Isolation of Stem and Progenitor Cells" Cells 9, no. 10: 2159. https://doi.org/10.3390/cells9102159

APA Style

Tolu, S. S., Wang, K., Yan, Z., Zhang, S., Roberts, K., Crouch, A. S., Sebastian, G., Chaitowitz, M., Fornari, E. D., Schwechter, E. M., Uehlinger, J., Manwani, D., Minniti, C. P., & Bouhassira, E. E. (2020). Characterization of Hematopoiesis in Sickle Cell Disease by Prospective Isolation of Stem and Progenitor Cells. Cells, 9(10), 2159. https://doi.org/10.3390/cells9102159

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