Grant: Operating Grant

Two groups of Canadians have to live with permanently dry mouths (xerostomia) because their salivary gland tissue have been injured or destroyed (about 160,000 who have Sjogren's syndrome, and patients who are receiving radiotherapy as part of their head and neck cancer treatment, which numbers approximate 4,000 new cases annually). These patients experience great discomfort in chewing and swallowing, sore throat, tooth decay, altered taste, and infections. At present there is no adequate treatment for irreversible salivary gland damage and these patients have to constantly sip water to reduce their discomfort a little. The aim of this research program is to offer to these patients effective treatment through the regeneration, replacement, and repair of salivary glands using cells (and their by-products) that are drawn from the patients' own tissues. Specifically, this proposal tests the efficacy of an extract from bone marrow cells (Bone marrow cell extract, BMCE) as a therapy to repair salivary glands damaged by irradiation or Sjogren's syndrome. We will assess the efficacy of BMCE in protecting salivary cells, increasing tissue neovascularization, function, and regeneration. This research is done in human salivary biopsies and in mouse models with irradiated salivary glands or with Sjogren's syndrome. The human salivary organotypic culture allows a longitudinal in situ observation of cellular and molecular events happening during irradiation injury and regeneration. The potential impact of regenerating lost salivary tissues is enormous. A long-term goal of this proposed work is to offer to millions of patients worldwide, having reduced or no saliva output (severe xerostomia), effective treatment options. These include the potential for regeneration and repair of saliva-secreting cells in adult glands.