Get access

Effects of pH on human bone marrow stromal cells in vitro: Implications for tissue engineering of bone

Authors

  • David H. Kohn,

    Corresponding author
    1. Department of Biologic and Materials Sciences, School of Dentistry, The University of Michigan, Ann Arbor, Michigan 48109-1078
    2. Department of Biomedical Engineering, College of Engineering, The University of Michigan, Ann Arbor, Michigan 48109-2125
    • Department of Biologic and Materials Sciences, School of Dentistry, The University of Michigan, Ann Arbor, Michigan 48109-1078
    Search for more papers by this author
  • Mojgan Sarmadi,

    1. Department of Oral Medicine, Pathology, and Oncology, School of Dentistry, The University of Michigan, Ann Arbor, Michigan 48109-1078
    Search for more papers by this author
  • Joseph I. Helman,

    1. Department of Oral and Maxillofacial Surgery, School of Dentistry, The University of Michigan, Ann Arbor, Michigan 48109-1078
    Search for more papers by this author
  • Paul H. Krebsbach

    Corresponding author
    1. Department of Oral Medicine, Pathology, and Oncology, School of Dentistry, The University of Michigan, Ann Arbor, Michigan 48109-1078
    • Department of Oral Medicine, Pathology, and Oncology, School of Dentistry, The University of Michigan, Ann Arbor, Michigan 48109-1078
    Search for more papers by this author

Abstract

The objective of this study was to address the hypothesis that changes in extracellular pH alter collagen gene expression, collagen synthesis, and alkaline phosphatase activity in bone marrow stromal cells (BMSCs). Potential effects of pH on cell function are of particular importance for tissue engineering because considerable effort is being placed on engineering biodegradable polymers that may generate a local acidic microenvironment on degradation. Human and murine single-cell marrow suspensions were plated at a density of 2 × 104 cells/cm2. After 7 days in culture, the pH of the culture medium was adjusted to one of six ranges: ≥7.8, 7.5.–7.7, 7.2–7.4, 6.9–7.1, 6.6–6.8, or ≤6.5. After 48 h of exposure to an altered pH, alkaline phosphatase activity and collagen synthesis decreased significantly with decreasing pH. This decrease was two-to threefold as pH decreased from 7.5 to 6.6. In contrast, α1(I) procollagen mRNA levels increased two- to threefold as pH was decreased. The trend in osteocalcin mRNA expression was opposite to that of collagen. Small shifts in extracellular pH led to significant changes in the ability of BMSCs to express markers of the osteoblast phenotype. These pH effects potentially relate to the microenvironment supplied by a tissue-engineering scaffold and suggest that degrading polymer scaffolds may influence the biologic activity of the cells in the immediate environment. © 2002 John Wiley & Sons, Inc. J Biomed Mater Res 60: 292–299, 2002; DOI 10.1002/jbm.10050

Ancillary