Calcified Tissue International

, Volume 82, Issue 1, pp 44–56 | Cite as

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

  • Pieter Steenhuis
  • Glenda J. Pettway
  • Michael A. IgnelziJr.
Article

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.

Keywords

Calvaria Sca-1 Magnetic cell sorting Osteoblast Stem cell Transplantation 

References

  1. 1.
    Opperman LA (2000) Cranial sutures as intramembranous bone growth sites. Dev Dyn 219:472–485PubMedCrossRefGoogle Scholar
  2. 2.
    Aguila HL, Weissman IL (1996) Hematopoietic stem cells are not direct cytotoxic targets of natural killer cells. Blood 87:1225–1231PubMedGoogle Scholar
  3. 3.
    Bachar-Lustig E, Li HW, Gur H, Krauthgamer R, Marcus H, Reisner Y (1999) Induction of donor-type chimerism and transplantation tolerance across major histocompatibility barriers in sublethally irradiated mice by Sca-1+Lin bone marrow progenitor cells: synergism with non-alloreactive (host x donor)F1 T cells. Blood 94:3212–3221PubMedGoogle Scholar
  4. 4.
    Bailey AS, Jiang S, Afentoulis M, Baumann CI, Schroeder DA, Olson SB, Wong MH, Fleming WH (2004) Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells. Blood 103:13–19PubMedCrossRefGoogle Scholar
  5. 5.
    Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF, Kunkel LM, Mulligan RC (1999) Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401:390–394PubMedGoogle Scholar
  6. 6.
    Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M (2000) Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6:1229–1234PubMedCrossRefGoogle Scholar
  7. 7.
    Spangrude GJ, Heimfeld S, Weissman IL (1988) Purification and characterization of mouse hematopoietic stem cells. Science 241:58–62PubMedCrossRefGoogle Scholar
  8. 8.
    Welm BE, Tepera SB, Venezia T, Graubert TA, Rosen JM, Goodell MA (2002) Sca-1(pos) cells in the mouse mammary gland represent an enriched progenitor cell population. Dev Biol 245:42–56PubMedCrossRefGoogle Scholar
  9. 9.
    Baddoo M, Hill K, Wilkinson R, Gaupp D, Hughes C, Kopen GC, Phinney DG (2003) Characterization of mesenchymal stem cells isolated from murine bone marrow by negative selection. J Cell Biochem 89:1235–1249PubMedCrossRefGoogle Scholar
  10. 10.
    Gojo S, Gojo N, Takeda Y, Mori T, Abe H, Kyo S, Hata J, Umezawa A (2003) In vivo cardiovasculogenesis by direct injection of isolated adult mesenchymal stem cells. Exp Cell Res 288:51–59PubMedCrossRefGoogle Scholar
  11. 11.
    Lee J, Kuroda S, Shichinohe H, Ikeda J, Seki T, Hida K, Tada M, Sawada K, Iwasaki Y (2003) Migration and differentiation of nuclear fluorescence-labeled bone marrow stromal cells after transplantation into cerebral infarct and spinal cord injury in mice. Neuropathology 23:169–180PubMedCrossRefGoogle Scholar
  12. 12.
    Peister A, Mellad JA, Larson BL, Hall BM, Gibson LF, Prockop DJ (2004) Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation, and differentiation potential. Blood 103:1662–1668PubMedCrossRefGoogle Scholar
  13. 13.
    Park J, Gelse K, Frank S, von der Mark K, Aigner T, Schneider H (2006) Transgene-activated mesenchymal cells for articular cartilage repair: a comparison of primary bone marrow-, perichondrium/periosteum- and fat-derived cells. J Gene Med 8:112–125PubMedCrossRefGoogle Scholar
  14. 14.
    Wolnicka-Glubisz A, King W, Noonan FP (2005) SCA-1+ cells with an adipocyte phenotype in neonatal mouse skin. J Invest Dermatol 125:383–385PubMedCrossRefGoogle Scholar
  15. 15.
    Van Vlasselaer P, Falla N, Snoeck H, Mathieu E (1994) Characterization and purification of osteogenic cells from murine bone marrow by two-color cell sorting using anti-Sca-1 monoclonal antibody and wheat germ agglutinin. Blood 84:753–763PubMedGoogle Scholar
  16. 16.
    Horowitz MC, Fields A, DeMeo D, Qian HY, Bothwell AL, Trepman E (1994) Expression and regulation of Ly-6 differentiation antigens by murine osteoblasts. Endocrinology 135:1032–1043PubMedCrossRefGoogle Scholar
  17. 17.
    Ito CY, Li CY, Bernstein A, Dick JE, Stanford WL (2003) Hematopoietic stem cell and progenitor defects in Sca-1/Ly-6A-null mice. Blood 101:517–523PubMedCrossRefGoogle Scholar
  18. 18.
    Bonyadi M, Waldman SD, Liu D, Aubin JE, Grynpas MD, Stanford WL (2003) Mesenchymal progenitor self-renewal deficiency leads to age-dependent osteoporosis in Sca-1/Ly-6A null mice. Proc Natl Acad Sci USA 100:5840–5845PubMedCrossRefGoogle Scholar
  19. 19.
    Mitchell PO, Mills T, O’Connor RS, Graubert T, Dzierzak E, Pavlath GK (2005) Sca-1 negatively regulates proliferation and differentiation of muscle cells. Dev Biol 283:240–252PubMedCrossRefGoogle Scholar
  20. 20.
    Epting CL, Lopez JE, Shen X, Liu L, Bristow J, Bernstein HS (2004) Stem cell antigen-1 is necessary for cell-cycle withdrawal and myoblast differentiation in C2C12 cells. J Cell Sci 117:6185–6195PubMedCrossRefGoogle Scholar
  21. 21.
    Bianco P, Riminucci M, Gronthos S, Robey PG (2001) Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19:180–192PubMedCrossRefGoogle Scholar
  22. 22.
    Krebsbach PH, Kuznetsov SA, Bianco P, Robey PG (1999) Bone marrow stromal cells: characterization and clinical application. Crit Rev Oral Biol Med 10:165–181PubMedCrossRefGoogle Scholar
  23. 23.
    Long MW (2001) Osteogenesis and bone-marrow-derived cells. Blood Cells Mol Dis 27:677–690PubMedCrossRefGoogle Scholar
  24. 24.
    Pettway GJ, Schneider A, Koh AJ, Widjaja E, Morris MD, Meganck JA, Goldstein SA, McCauley LK (2005) Anabolic actions of PTH (1–34): use of a novel tissue engineering model to investigate temporal effects on bone. Bone 36:959–970PubMedCrossRefGoogle Scholar
  25. 25.
    Rosen ED, Spiegelman BM (2000) Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol 16:145–171PubMedCrossRefGoogle Scholar
  26. 26.
    Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–764PubMedCrossRefGoogle Scholar
  27. 27.
    Stein GS, Lian JB, van Wijnen AJ, Stein JL, Montecino M, Javed A, Zaidi SK, Young DW, Choi JY, Pockwinse SM (2004) Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression. Oncogene 23:4315–4329PubMedCrossRefGoogle Scholar
  28. 28.
    Steenhuis P, Carr KM, Pettway GJ, Ignelzi MA Stem/Progenitor Cells Isolated From Postnatal Mouse Calvaria. Unpublished resultsGoogle Scholar
  29. 29.
    Wang J, Glimcher MJ (1999) Characterization of matrix-induced osteogenesis in rat calvarial bone defects: II. Origins of bone-forming cells. Calcif Tissue Int 65:486–493PubMedCrossRefGoogle Scholar
  30. 30.
    Opperman LA, Passarelli RW, Morgan EP, Reintjes M, Ogle RC (1995) Cranial sutures require tissue interactions with dura mater to resist osseous obliteration in vitro. J Bone Miner Res 10:1978–1987PubMedCrossRefGoogle Scholar
  31. 31.
    Opperman LA, Sweeney TM, Redmon J, Persing JA, Ogle RC (1993) Tissue interactions with underlying dura mater inhibit osseous obliteration of developing cranial sutures. Dev Dyn 198:312–322PubMedGoogle Scholar
  32. 32.
    Mabbutt LW, Kokich VG (1979) Calvarial and sutural re-development following craniectomy in the neonatal rabbit. J Anat 129:413–422PubMedGoogle Scholar
  33. 33.
    Mabbutt LW, Kokich VG, Moffett BC, Loeser JD (1979) Subtotal neonatal calvariectomy. A radiographic and histological evaluation of calvarial and sutural redevelopment in rabbits. J Neurosurg 51:691–696PubMedGoogle Scholar
  34. 34.
    Hobar PC, Schreiber JS, McCarthy JG, Thomas PA (1993) The role of the dura in cranial bone regeneration in the immature animal. Plast Reconstr Surg 92:405–410PubMedCrossRefGoogle Scholar
  35. 35.
    Drake DB, Persing JA, Berman DE, Ogle RC (1993) Calvarial deformity regeneration following subtotal craniectomy for craniosynostosis: a case report and theoretical implications. J Craniofac Surg 4:85–90PubMedCrossRefGoogle Scholar
  36. 36.
    Hutmacher DW, Sittinger M (2003) Periosteal cells in bone tissue engineering. Tissue Eng 9 Suppl 1:S45–S64PubMedCrossRefGoogle Scholar
  37. 37.
    Nakahara H, Bruder SP, Goldberg VM, Caplan AI (1990) In vivo osteochondrogenic potential of cultured cells derived from the periosteum. Clin Orthop Relat Res 259:223–232PubMedGoogle Scholar
  38. 38.
    Aubin JE (1999) Osteoprogenitor cell frequency in rat bone marrow stromal populations: role for heterotypic cell–cell interactions in osteoblast differentiation. J Cell Biochem 72:396–410PubMedCrossRefGoogle Scholar
  39. 39.
    Purpura KA, Zandstra PW, Aubin JE (2003) Fluorescence activated cell sorting reveals heterogeneous and cell non-autonomous osteoprogenitor differentiation in fetal rat calvaria cell populations. J Cell Biochem 90:109–120PubMedCrossRefGoogle Scholar
  40. 40.
    Eipers PG, Kale S, Taichman RS, Pipia GG, Swords NA, Mann KG, Long MW (2000) Bone marrow accessory cells regulate human bone precursor cell development. Exp Hematol 28:815–825PubMedCrossRefGoogle Scholar
  41. 41.
    Stewart K, Monk P, Walsh S, Jefferiss CM, Letchford J, Beresford JN (2003) STRO-1, HOP-26 (CD63), CD49a and SB-10 (CD166) as markers of primitive human marrow stromal cells and their more differentiated progeny: a comparative investigation in vitro. Cell Tissue Res 313:281–290PubMedCrossRefGoogle Scholar
  42. 42.
    Goodell MA, McKinney-Freeman S, Camargo FD (2004) Isolation and characterization of side population cells. Methods Mol Biol 290:343–352Google Scholar
  43. 43.
    Smith JD, Abramson M (1974) Membranous vs. endochondral bone autografts. Arch Otolaryngol 99:203–205PubMedGoogle Scholar
  44. 44.
    Zins JE, Whitaker LA (1983) Membranous versus endochondral bone: implications for craniofacial reconstruction. Plast Reconstr Surg 72:778–785PubMedCrossRefGoogle Scholar
  45. 45.
    Tessier P (1982) Autogenous bone grafts taken from the calvarium for facial and cranial applications. Clin Plast Surg 9:531–538PubMedGoogle Scholar
  46. 46.
    Hunter D, Baker S, Sobol SM (1990) Split calvarial grafts in maxillofacial reconstruction. Otolaryngol Head Neck Surg 102:345–350PubMedGoogle Scholar
  47. 47.
    Frodel JL Jr, Marentette LJ, Quatela VC, Weinstein GS (1993) Calvarial bone graft harvest. Techniques, considerations, and morbidity. Arch Otolaryngol Head Neck Surg 119:17–23PubMedGoogle Scholar
  48. 48.
    Carinci F, Farina A, Zanetti U, Vinci R, Negrini S, Calura G, Laino G, Piattelli A (2005) Alveolar ridge augmentation: a comparative longitudinal study between calvaria and iliac crest bone grafrs. J Oral Implantol 31:39–45PubMedCrossRefGoogle Scholar
  49. 49.
    Cinberg JZ, Rosenbaum FA, Lowrie C, Gorman M (1985) Calvarial grafts for midface rehabilitation. Arch Otolaryngol 111:434–436PubMedGoogle Scholar
  50. 50.
    Maves MD, Matt BH (1986) Calvarial bone grafting of facial defects. Otolaryngol Head Neck Surg 95:464–470PubMedGoogle Scholar
  51. 51.
    Smolka W, Eggensperger N, Kollar A, Iizuka T (2005) Midfacial reconstruction using calvarial split bone grafts. Arch Otolaryngol Head Neck Surg 131:131–136PubMedCrossRefGoogle Scholar
  52. 52.
    Frodel JL (1999) Calvarial bone graft harvest in children. Otolaryngol Head Neck Surg 121:78–81PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Pieter Steenhuis
    • 1
    • 3
  • Glenda J. Pettway
    • 2
  • Michael A. IgnelziJr.
    • 1
  1. 1.Department of Orthodontics and Pediatric DentistryUniversity of Michigan School of DentistryAnn ArborUSA
  2. 2.Department of Periodontics and Oral Medicine, School of Dentistry, and Department of Biomedical Engineering, College of EngineeringUniversity of MichiganAnn ArborUSA
  3. 3.Department of DermatologyUniversity of California DavisDavisUSA

Personalised recommendations