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c-Kit Expression and Stem Cell Factor-Induced Hematopoietic Cell Proliferation Are Up-Regulated in Aged B6D2F1 Mice

¹ Hematology Branch
² Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.

Address correspondence to Dr. Jichun Chen, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Clinical Research Center Room 3-5132, 10 Center Drive, Bethesda, MD 20892-1202. E-mail: chenji{at}nhlbi.nih.gov

Expression of c-Kit (CD117) and stem cell factor/c-Kit-mediated cell proliferation were tested in vitro in young and old B6D2F1 mice to study the role of c-Kit signaling in hematopoietic stem cell (HSC) senescence. Increasing age is associated with a significant increase in bone marrow (BM) cells without affecting mature blood cells. The number of c-Kit-expressing BM cells increased significantly in old mice when compared to young controls, to 201% in total BM cells, 261% in Lin^– cells, 517% in Lin^–CD34⁺Sca1⁺ progenitor cells, and 1272% in Lin^–CD34^–Sca1⁺ HSCs. Sorted Lin^–Sca1⁺CD117⁺ BM cells from an old mouse expanded 5-fold when cultured in vitro for 72 hours with stem cell factor at 25 ng/ml, which was significantly higher than a 2.5-fold expansion of the same cells from a young donor. HSCs and progenitor cells from B6D2F1 mice maintain extremely high proliferative potentials and do not reach proliferative arrest at old age during a normal life span.