Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells: Correlation with cytokines

Abstract

Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N = 100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non-significantly. IGF-1 levels (mean = 30.7, SEM = 2) decreased and IL-6 levels (mean = 4.4, SEM = 1) increased with age as did marrow fat (mean = 1.2 mm fat/g, SEM = 0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive.

Changes of number of cells expressing proliferation and progenitor cell markers with age in rabbit intervertebral discs

“…The concept that migrating progenitor cell from stem cell niches contribute to normal regeneration of IVD has also been supported by a recent report [6]. The number of hematopoietic stem cells decreases with aging both in mouse [33] and human bone marrow [34]. Also in vertebra the mesenchymal stromal stem cells were found to decrease with age, which may be the responsible for the age-related osteoporosis [35].…”

Height indicates hematopoietic capacity in elderly Japanese men

“…The side population of hematopoietic stem cells in the bone marrow decreases as individuals age [18,19], which may be associated with increased frequency of anemia seen in the elderly [20]. Neumann reported a decline in active hematopoietic (red) bone marrow with age and transformation into fatty (yellow) marrow from the periphery towards the axial skeleton [13].…”

Impacts of age and gender on bone marrow profiles of BMP7, BMPRs and Stro-1+ cells in patients with total hip replacement

“…There is a lower number of BMSC Stro-1 + cells in old rats than that of younger rats [23]. Many clinical variables might contribute to the variations in the number of BMSC Stro-1 + cells, including the age and gender of the subjects [8,9]. In addition, one cannot exclude the possibility that some of the age-related changes we have found could relate to BMSC Stro-1 + expression, which is associated with osteoarthritis, and this should be considered [24,25].…”

“…The bone marrow Stro-1 + is capable of differentiating into multiple mesenchymal lineages including adipocytes, osteoblasts, and chondrocytes [6,8]. The variation of Stro-1 + cells can be observed between human subjects [9]. However, the impact of age and gender on the population of Stro-1 + cells has not been well studied.…”