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

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dc.citation.journalTitleStem Cells Translational Medicineen_US
dc.citation.volumeNumber5en_US
dc.contributor.authorSrinivasan, Padma Pradeepaen_US
dc.contributor.authorPatel, Vaishali N.en_US
dc.contributor.authorLiu, Shuangen_US
dc.contributor.authorHarrington, Daniel Antonen_US
dc.contributor.authorHoffman, Matthew P.en_US
dc.contributor.authorJia, Xinqiaoen_US
dc.contributor.authorWitt, Robert L.en_US
dc.contributor.authorFarach-Carson, Mary C.en_US
dc.contributor.authorPradhan-Bhatt, Swatien_US
dc.contributor.orgBioengineeringen_US
dc.contributor.orgBiosciencesen_US
dc.date.accessioned2017-01-27T22:23:42Zen_US
dc.date.available2017-01-27T22:23:42Zen_US
dc.date.issued2016en_US
dc.description.abstractRadiotherapy 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 to engineer functional, three-dimensional (3D) salivary gland neotissue for autologous implantation to provide permanent relief. An immediate need exists to obtain autologous adult progenitor cells as the use of embryonic and induced pluripotent stem cells potentially pose serious risks such as teratogenicity and immunogenic rejection. Here, we report an expandable population of primary salivary human stem/progenitor cells (hS/PCs) that can be reproducibly and scalably isolated and propagated from tissue biopsies. These cells have increased expression of progenitor markers (K5, K14, MYC, ETV4, ETV5) compared with differentiation markers of the parotid gland (acinar: MIST1/BHLHA15 and AMY1A; ductal: K19 and TFCP2L1). Isolated hS/PCs grown in suspension formed primary and secondary spheres and could be maintained in long-term 3D hydrogel culture. When grown in a customized 3D modular hyaluronate-based hydrogel system modified with bioactive basement membrane-derived peptides, levels of progenitor markers, indices of proliferation, and viability of hS/PCs were enhanced. When appropriate microenvironmental cues were provided in a controlled manner in 3D, such as stimulation with β-adrenergic and cholinergic agonists, hS/PCs differentiated into an acinar-like lineage, needed for saliva production. We conclude that the stem/progenitor potential of adult hS/PCs isolated without antigenic sorting or clonal expansion in suspension, combined with their ability to differentiate into specialized salivary cell lineages in a human-compatible culture system, makes them ideal for use in 3D bioengineered salivary gland applications.en_US
dc.identifier.citationSrinivasan, Padma Pradeepa, Patel, Vaishali N., Liu, Shuang, et al.. "Primary Salivary Human Stem/Progenitor Cells Undergo Microenvironment-Driven Acinar-Like Differentiation in Hyaluronate Hydrogel Culture." <i>Stem Cells Translational Medicine,</i> 5, (2016) AlphaMed Press: http://dx.doi.org/10.5966/sctm.2016-0083.en_US
dc.identifier.doihttp://dx.doi.org/10.5966/sctm.2016-0083en_US
dc.identifier.urihttps://hdl.handle.net/1911/93799en_US
dc.language.isoengen_US
dc.publisherAlphaMed Pressen_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.subject.keywordSalivary glandsen_US
dc.subject.keywordStem/progenitor cellsen_US
dc.subject.keywordHyaluronic aciden_US
dc.subject.keywordTissue engineeringen_US
dc.subject.keywordThree-dimensional hydrogel cultureen_US
dc.titlePrimary Salivary Human Stem/Progenitor Cells Undergo Microenvironment-Driven Acinar-Like Differentiation in Hyaluronate Hydrogel Cultureen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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