Age-related changes in osteogenic stem cells in mice

Abstract

Osteoblasts arise from partially differentiated osteogenic progenitor cells (OPCs) which in turn arise from undifferentiated marrow stromal mesenchymal stem cells (MSCs). It has been postulated that age-related defects in osteoblast number and function may be due to quantitative and qualitative stem cell defects. To examine this possibility, we compared osteogenic stem cell number and in vitro function in marrow cells from 4-month-old and 24-month-old male BALB/c mice. Histologic studies demonstrated that these mice undergo age-related bone loss resembling that seen in humans. In primary MSC cultures grown in media supplemented with 10 nM dexamethasone, cultures from older animals yielded an average of 41% fewer OPC colonies per given number of marrow cells plated (p < 0.001). This implies that for a given number of marrow cells there are fewer stem cells with osteogenic potential in older animals than there are in younger animals. The basal proliferative rate in cultures from older animals, as measured by 3H-thymidine uptake, was more than three times that observed in cultures from young animals (p < 0.005). However, the increase in proliferative response to serum stimulation was 10-fold in the younger cultures (p <0.001) and insignificant (p <0.4) in the older cultures. Colonies in both age groups became alkaline phosphatase positive at the same rate, and virtually all colonies were positive after 12 days of culture. Cultures from both age groups produced abundant type I collagen. These studies suggest that defects in the number and proliferative potential of MSCs may underlie age-related defects in osteoblast number and function.

Isolation, characterization and differentiation of mesenchymal stem cells from amniotic fluid, umbilical cord blood and Wharton's jelly in the horse

“…Recently, Stolzing et al (2008) confirmed those already demonstrated in previous studies (D 'Ippolito et al 1999, Mendes et al 2002, Chen et al 2005, Zhang et al 2005, Zheng et al 2007, Kretlow et al 2008, observing a significant age-related change in membrane markers expression levels, an alkaline phosphatase activity, chondrogenic and myogenic differentiation potency decline with donor age in contrast with adipogenic differentiation. However, these data are in contrast with those reported by other research groups (Bergman et al 1996, Stenderup et al 2001, Bellows et al 2003, which showed no age-related differences in differentiation potency. Different results obtained are with regard to the choice of age groups, group size, gender, inclusion of pathological states, isolation and cultivation conditions (Sethe et al 2006).…”

Changes in chondrogenic phenotype and gene expression profiles associated with the in vitro expansion of human synovium‐derived cells

“…Reports about multipotency of MSCs in relation to donor age or osteoarthritis are conflicting. Some suggest a decrease in differentiation capacity with age or osteoarthritis, 13,43,44 whereas others suggest no such relation. 35,45,46 Therefore, our findings may not relate to MSCs from young healthy donors.…”

“…The number of MSCs produced by primary culture is limited, which may reflect underlying agerelated defects. 13,14 Thus, in vitro expansion is needed. However, BM-MSCs lose their proliferative and differential potentials when subjected to repeated in vitro culture, a concern for their clinical applications.…”

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…Models that are better understood and described in the literature often have proven records of being more predictive of clinical outcomes. The age of study animals as well as gender can influence the bone repair through the action of calciotropic hormones and thus merit careful consideration [115][116][117][118][119]. For example, aged, thyroparathyroidectomized and ovariectomized (OVX) animals are known for delayed fracture healing and reduced bone mineral density; therefore, OVX animals are frequently utilized to study osteoporotic fractures because these models mimic postmenopausal women [88,120,121].…”