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Cell Surface Expression of Stem Cell Antigen-1 (Sca-1) Distinguishes Osteo-, Chondro-, and Adipoprogenitors in Fetal Mouse Calvaria

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Abstract

The flat bones of the skull (calvaria) develop by balanced cell proliferation and differentiation in the calvarial sutures and the bone tips. As the brain grows and the calvaria expand, cells within the sutures must remain undifferentiated to maintain suture patency, but osteoprogenitors also need to be recruited into the osteogenic fronts. The exact identity of calvarial osteoprogenitors is currently not known. We used immunomagnetic cell sorting to isolate Sca-1+ and Sca-1− cells from fetal mouse calvaria and determined their differentiation potential in in vitro differentiation asssays and in vivo subcutaneous transplantations. Cells within the Sca-1+ cell fraction have a higher adipogenic potential, whereas cells within the Sca-1− cell fraction have a higher osteogenic and chondrogenic potential. The Sca-1− fraction retains its chondrogenic potential after in vitro expansion but not its osteogenic potential. The Sca-1+ fraction does not retain its adipogenic potential after in vitro expansion. Subcutaneous transplantation resulted in islands of bone and cartilage in implants that had been seeded with Sca-1− cells. In conclusion, immunomagnetic cell sorting with Sca-1 antibodies can be used to separate a Sca-1+ cell fraction with adipogenic potential from a Sca-1− cell fraction with osteogenic and chondrogenic potential. Isolation of pure populations of calvarial adipoprogenitors, osteoprogenitors, and chondroprogenitors will be beneficial for cellular studies of calvarial development, adipogenesis, osteogenesis, and chondrogenesis. Calvaria-derived osteogenic cell populations may be useful in craniofacial tissue regeneration and repair.

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Acknowledgement

We thank Laurie K. McCauley and Michael W. Long for valuable discussions and Kathy Welch for advice on statistical methods. This study was supported by the National Institutes of Health (DE11530).

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Authors and Affiliations

  1. Department of Orthodontics and Pediatric Dentistry, University of Michigan School of Dentistry, 1011 North University Avenue, Ann Arbor, MI, 48109-1078, USA

    Pieter Steenhuis & Michael A. Ignelzi Jr.

  2. Department of Periodontics and Oral Medicine, School of Dentistry, and Department of Biomedical Engineering, College of Engineering, University of Michigan, 1011 North University Avenue, Ann Arbor, MI, 48109-1078, USA

    Glenda J. Pettway

  3. Department of Dermatology, University of California Davis, 1 Shields Avenue, TB205, Room 102, Davis, CA, 95616-5270, USA

    Pieter Steenhuis

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  1. Pieter Steenhuis
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Correspondence to Pieter Steenhuis.

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Steenhuis, P., Pettway, G.J. & Ignelzi, M.A. Cell Surface Expression of Stem Cell Antigen-1 (Sca-1) Distinguishes Osteo-, Chondro-, and Adipoprogenitors in Fetal Mouse Calvaria. Calcif Tissue Int 82, 44–56 (2008). https://doi.org/10.1007/s00223-007-9083-4

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