Direct comparison of progenitor cells derived from adipose, muscle, and bone marrow from wild-type or craniosynostotic rabbits.

BACKGROUND: Reports have identified cells capable of osteogenic differentiation in bone marrow, muscle, and adipose tissues, but there are few direct comparisons of these different cell types. Also, few have investigated the potential connection between a tissue-specific abnormality and cells derived from seemingly unrelated tissues. In this article, the authors compare cells isolated from wild-type rabbits or rabbits with nonsyndromic craniosynostosis, defined as the premature fusion of one or more of the cranial sutures. METHODS: Cells were derived from bone marrow, adipose, and muscle of 10-day-old wild-type rabbits (n = 17) or from age-matched rabbits with familial nonsyndromic craniosynostosis (n = 18). Cells were stimulated with bone morphogenetic protein-4 (BMP4), and alkaline phosphatase expression and cell proliferation were assessed. RESULTS: In wild-type rabbits, cells derived from muscle had more alkaline phosphatase activity than cells derived from either adipose or bone marrow. The cells derived from craniosynostotic rabbit bone marrow and muscle were significantly more osteogenic than those derived from wild-type rabbits. Adipose-derived cells demonstrated no significant differences. Although muscle-derived cells were most osteogenic in wild-type rabbits, bone marrow-derived cells were most osteogenic in craniosynostotic rabbits. CONCLUSIONS: These results suggest that cells from different tissues have different potentials for differentiation. Furthermore, cells derived from rabbits with craniosynostosis were different from cells from wild-type rabbits. Interestingly, cells derived from the craniosynostotic rabbits were not uniformly more responsive compared with wild-type cells, suggesting that specific tissue-derived cells may react differently in individuals with craniosynostosis.

BMP-4 response in wild-type and craniosynostotic rabbit bone cells.

BACKGROUND: Craniosynostosis results from improper regulation of bone formation. Investigations of cells derived from patients with craniosynostosis suggest that craniosynostotic bone-derived cells have increased osteogenic or proliferative capacities compared with other cells. Research into the pathogenesis of craniosynostosis using cells derived from children has been hindered by small sample sizes and inappropriate control cell populations. The authors hypothesized that cells derived from suture-associated regions of bone from craniosynostotic rabbits were more osteogenic and proliferative than bone cells derived from wild-type rabbits. METHODS: This study used cells derived from a colony of rabbits with congenital, nonsyndromic craniosynostosis (n = 20) or from age-matched wild-type rabbits (n = 20). Bone cells derived from either suture-associated or non-suture-associated bone were challenged with osteogenic stimuli and assessed for osteogenic differentiation. RESULTS: The results suggest a high level of variability among cells derived from different individual rabbits. Also, craniosynostotic bone cells have a larger response to recombinant human bone morphogenetic protein 4 stimulation relative to baseline expression of alkaline phosphatase, although overall alkaline phosphatase expression was higher in wild-type bone cells. Cell proliferation showed some differences at 3 days in culture, but no differences were found at 7 days in culture. CONCLUSIONS: This study suggests that bone cells in this rabbit model of craniosynostosis are generally similar to wild-type cells. Also, because of variability, it is necessary to have larger sample sizes than are normally available in human studies. Therefore, cells from the rabbit model may be a powerful in vitro model for further craniosynostosis research.