Primary Salivary Human Stem/Progenitor Cells Undergo Microenvironment-Driven Acinar-Like Differentiation in Hyaluronate Hydrogel Culture

摘要: Radiotherapy for head and neck cancer often has undesirable effects on salivary glands that lead to xerostomia or severe dry mouth, which can increase oral infections. Our goal is engineer functional, three-dimensional (3D) gland neotissue autologous implantation provide permanent relief. An immediate need exists obtain adult progenitor cells as the use of embryonic induced pluripotent stem potentially pose serious risks such teratogenicity immunogenic rejection. Here, we report an expandable population primary human stem/progenitor (hS/PCs) be reproducibly scalably isolated propagated from tissue biopsies. These have increased expression markers (K5, K14, MYC, ETV4, ETV5) compared with differentiation parotid (acinar: MIST1/BHLHA15 AMY1A; ductal: K19 TFCP2L1). Isolated hS/PCs grown in suspension formed secondary spheres could maintained long-term 3D hydrogel culture. When a customized modular hyaluronate-based system modified bioactive basement membrane-derived peptides, levels markers, indices proliferation, viability were enhanced. appropriate microenvironmental cues provided controlled manner 3D, stimulation β-adrenergic cholinergic agonists, differentiated into acinar-like lineage, needed saliva production. We conclude potential without antigenic sorting clonal expansion suspension, combined their ability differentiate specialized cell lineages human-compatible culture system, makes them ideal bioengineered applications. Stem Cells Translational Medicine 2017;6:110-120.