Stem Cell–Soluble Signals Enhance Multilumen Formation in SMG Cell Clusters

• Published in: Journal of dental research 2015-11, Vol.94 (11), p.1610-1617
• Main Authors: Maruyama, C.L.M., Leigh, N.J., Nelson, J.W., McCall, A.D., Mellas, R.E., Lei, P., Andreadis, S.T., Baker, O.J.
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors (muscarinic); Acinar cells; Animals; Aquaporin 5 - physiology; Cell differentiation; Cell Differentiation - physiology; Cell growth; Chewing; Compliance; Data analysis; Dentistry; Epidermal growth factor; Female; Hair Follicle - cytology; Humans; Hydrogels; Insulin-like growth factors; Laminin; Laminin - physiology; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - physiology; Mesenchyme; Mice, Inbred C57BL; Microscopy; Peptides; Periodontal diseases; Pilocarpine; Quality of life; Research Reports; Saliva; Salivary Ducts - cytology; Salivary Ducts - growth & development; Salivary gland; Salivary Glands - cytology; Salivary Glands - growth & development; Secretion; Stem cell transplantation; Stem cells; Studies; Submandibular Gland - cytology; Submandibular Gland - physiology; Swallowing; Tissue Engineering - methods
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/0022034515600157

Saliva plays a major role in maintaining oral health. Patients with salivary hypofunction exhibit difficulty in chewing and swallowing foods, tooth decay, periodontal disease, and microbial infections. At this time, treatments for hyposalivation are limited to medications (e.g., muscarinic receptor agonists: pilocarpine and cevimeline) that induce saliva secretion from residual acinar cells as well as artificial salivary substitutes. Therefore, advancement of restorative treatments is necessary to improve the quality of life in these patients. Our previous studies indicated that salivary cells are able to form polarized 3-dimensional structures when grown on growth factor–reduced Matrigel. This basement membrane is rich in laminin-III (L1), which plays a critical role in salivary gland formation. Mitotically inactive feeder layers have been used previously to support the growth of many different cell types, as they provide factors necessary for cell growth and organization. The goal of this study was to improve salivary gland cell differentiation in primary cultures by using a combination of L1 and a feeder layer of human hair follicle–derived mesenchymal stem cells (hHF-MSCs). Our results indicated that the direct contact of mouse submandibular (mSMG) cell clusters and hHF-MSCs was not required for mSMG cells to form acinar and ductal structures. However, the hHF-MSC conditioned medium enhanced cell organization and multilumen formation, indicating that soluble signals secreted by hHF-MSCs play a role in promoting these features.