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Quiescence has been thought to be required for the retention of the full biological potential of pluripotent hematopoietic stem cells (PHSCs). This hypothesis has been challenged recently by the observation that all murine PHSCs cycle continuously and constantly contribute to steadystate blood cell production. It was asked whether these observations could be extrapolated to describe hematopoiesis in higher mammals. In this series of experiments, the replicative history of PHSCs was examined in baboons by continuously administering bromodeoxyuridine (BrdU) for more than 85 weeks. The results indicate that under steady-state conditions, PHSCs remain largely quiescent but do cycle, albeit at a far lower rate than previously reported for rodent PHSCs. BrdU-labeled cycling PHSCs and progenitor cells were shown to have an extensive proliferative capacity and to contribute to blood cell production for prolonged periods of time. The proportion of PHSCs entering cell cycle could, however, be rapidly increased by the in vivo administration of granulocyte-colony stimulating factor. These data indicate that dur- IntroductionMammalian blood cell production is a tightly regulated process in which a hierarchy of cycling hematopoietic stem cell populations contributes to active hematopoiesis. [1][2][3][4][5] The formed elements of blood ultimately originate from rare pluripotent hematopoietic stem cells (PHSCs), which are capable of self-renewal and differentiation into cells belonging to each hematopoietic lineage. 6,7 PHSCs contribute to steady-state hematopoiesis and respond to a variety of stressful conditions without actually depleting their number. It is commonly believed that PHSCs remain quiescent during steady-state hematopoiesis and that stem cell quiescence plays a pivotal role in determining the self-renewal and proliferative potential of PHSCs. 8,9 In 1965, Kay 10 postulated that only a few PHSC clones actively contribute to blood cell production at any given time and that only after exhaustion of these active clones would additional PHSCs self-replicate and actively contribute to blood cell production. Experimental evidence supporting this clonal succession hypothesis was first gained by studies of the contribution of murine blood cell production by PHSCs that had been genetically modified by retroviral vectors. 11,12 The contribution of individual PHSCs to blood cell production was monitored by tracking retroviral integration sites in mature blood cells. Abkowitz and coworkers 13 also addressed this hypothesis by performing stem cell transplants in female cats who were heterozygotes for the X-linked gene glucose 6-phosphate dehydrogenase. They observed wide fluctuations in clonal contributions to hematopoiesis following initial engraftment but found that long-term reconstitution was due to a limited number of stem cell clones. 13 The validity of such reconstitution assays as an appropriate test of the clonal succession hypothesis has been questioned since the kinetics of hematopoietic reconstitution following st...

In recent years, the emphasis on aging research, has led to an increase in the number of aged macaques being maintained in some research facilities with a subsequent increase in the occurrence of age-related diseases. One of the most commonly reported age related diseases is intestinal adenocarcinoma. At the University of Illinois at Chicago (UIC), which maintains a colony of approximately 55 aged rhesus macaques 13 cases of intestinal adenocarcinoma were diagnosed within a 25-month period. This report provides a comprehensive description of the clinical findings for intestinal adenocarcinoma in aged rhesus macaques, including results from physical examinations, laboratory tests, radiographic evaluations, gross and histopathologic findings as well as a comparison with the disease condition in humans. The use of carcinoembryonic antigen as a potential tumor marker was evaluated by immunohistochemical analysis of tissue specimens in 10 cases. Intestinal adenocarcinoma is a disease condition that should be of concern to individuals responsible for the care of aged rhesus macaques.