Tissue Engineering of Functional Salivary Gland Tissue

Authors

  • Akira Joraku MD,

    1. Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
    Search for more papers by this author
  • Christopher A. Sullivan MD,

    Corresponding author
    1. Department of Otolaryngology—Head and Neck Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
    • Dr. Christopher A. Sullivan, Wake Forest University, School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-0001, U.S.A.
    Search for more papers by this author
  • James J. Yoo MD,

    1. Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
    Search for more papers by this author
  • Anthony Atala MD

    1. Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
    Search for more papers by this author

  • Presented at the Combined Otolaryngological Society Meeting, Phoenix, AZ, May 3, 2004.

    Drs. Akira Joraku, MD, and Christopher A. Sullivan, MD, contributed equally to this Manuscript.

    Source of funding: Wake Forest Institute for Regenerative Medicine.

Abstract

Objectives: Treatment of conditions that lead to salivary hypofunction, such as radiation induced xerostomia, is currently limited to the administration of saliva substitutes and sialogogues. The transient effect of these medications necessitates frequent administration, and systemic side effects may be intolerable. The creation of implantable, functional salivary gland tissue from autologous glandular cells would provide a physiologic solution to this problem. We investigated the feasibility of engineering such tissue in vivo.

Methods: Primary human salivary gland cells were grown, expanded, and seeded on biodegradable polymer scaffolds. A total of 48 scaffolds with cells and 16 control polymers without cells were implanted subcutaneously in athymic mice. The implants were retrieved 2, 4, and 8 weeks after the implantation for phenotypic and functional analyses.

Results: Human salivary gland epithelial cells retained their phenotypic and functional characteristics at all culture stages. Histologically, formation of acinar gland-like structures was observed within the engineered tissue by 4 weeks after implantation. Immunocytochemical and Western blot analyses of the implanted tissues demonstrated the expression of human a-amylase, cytokeratins AE1/AE3, and aquaporin-5 using cell-specific antibodies. Reverse-transcription polymerase chain reaction analyses confirmed the expression of human salivary type of α-amylase (σ-amylase) mRNA. The retrieved tissues demonstrated the production of human α-amylase over time using a biochemical amylase detection system.

Ancillary