Open AccessCaptopril Inhibits the Proliferation of Hematopoietic Stem and Progenitor Cells in Murine Long‐Term Bone Marrow Cultures
Author(s) -
Chisi John Eugenes,
WdzieczakBakala Joanna,
Thierry Josiane,
Briscoe Cecile V.,
Riches Andrew C.
Publication year - 1999
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.170339
Subject(s) - biology , haematopoiesis , progenitor cell , bone marrow , captopril , stem cell , immunology , cancer research , progenitor , microbiology and biotechnology , endocrinology , blood pressure
Drugs used mainly for the treatment of hypertension, such as angiotensin I‐converting enzyme (ACE) inhibitors, can cause pancytopenia. The underlying cause of this side effect remains unknown. In the present study, long‐term bone marrow cultures (LTBMCs) were utilized to evaluate the role of captopril (D‐3‐mercapto‐2‐methylpropionyl‐L‐proline), one of the potent ACE inhibitors, in regulating hematopoietic stem/progenitor cell proliferation. Captopril (10 −6 M final concentration) was added to LTBMCs at the beginning of the culture period and at weekly intervals for six weeks. There was no toxicity to the bone marrow cells as measured by the unchanged cell number in the nonadherent layer during the whole culture period, and there was an increased cellularity of the adherent layer at the end of the six weeks of treatment. However, captopril decreased the proportion of granulocyte‐macrophage colony‐forming cells (GM‐CFCs) in S phase at weeks 2 and 3 as well as that of high proliferative potential colony‐forming cells (HPP‐CFCs) at week 3 in the nonadherent layer. There was no change in the kinetics of the GM‐CFCs and HPP‐CFCs present in the adherent layer. These results suggest that captopril causes myelosuppression by inhibiting hematopoietic cell proliferation of progenitor and stem cells rather than depleting cells of the bone marrow microenvironment.