Three percent of all malignancies in the United States consist of head and neck cancers. Over 30,000 patients each year undergo therapeutic irradiation of the head and neck. Patients with cancer of the upper respiratory tract who receive radiotherapy suffer from xerostomia. Direct radiation damage of the acinar cells that secrete fluid and protein results in salivary gland hypofunction. The quantity and quality of saliva are severely altered and conditions such as xerostomia, dysphagia, dental caries, mucositis and oropharyngeal infections result. Thus, the quality of life of these patients significantly deteriorates. The goal of this project is to engineer a functional artificial salivary gland that can be implanted into patients suffering from xerostomia.
Figure 1: Domain IV of perlecan showing the location of PlnDIV peptide, TWSKVGGHLRPGIVQSG. Courtesy of M. C. Farach-Carson.
Our research involves obtaining salivary gland tissue specimens from patients undergoing routine salivary gland surgery. Parallels between biomarkers expressed in the salivary gland tissue and those retained by the cultured cells can be observed. Cultured sub-populations of acinar cells that expressed these tissue markers were capable of self-assembly. Salivary acinar cells grown on Matrigel™ or a peptide derived from domain IV of Perlecan (PlnDIV peptide) (Fig.1) were observed to support self-assembly into large lobular acini-like structures and abundantly expressed α-amylase, a salivary enzyme (Fig. 2). Efforts to devise a three-dimensional culture system consisting of a porous biodegradable scaffold with polarized acinar cells capable of secreting salivary fluid are underway.
Figure 2: PlnDIV peptide or Matrigel™ trigger differentiation of salivary gland cells into three-dimensional acini-like structures expressing α-amylase. Pradhan S. et. al. Perlecan domain IV peptide stimulates salivary gland cell assembly in vitro. (2009) Tissue Engineering Part A. Epub ahead of print.
