Generation of functional salivary gland tissue from human submandibular gland stem/progenitor cells

Sui, Yi; Zhang, Siqi; Li, Yongliang; Zhang, Xin; Hu, Waner; Yao, Feng; Xiong, Jing-Wei; Zhang, Yuanyuan; Wei, Shicheng

doi:10.1186/s13287-020-01628-4

Cited by 46 publications

(56 citation statements)

References 37 publications

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“…MBs also allow long-term cell culture, and the ability to fabricate them in high-density arrays (>4000 MB/cm 2 ) provides a useful platform for high-throughput and high-content screening 44 . In contrast to many tissue chip formats, this approach does not rely on stem cells or iPSCs, but on mature, fully differentiated salivary gland cell types, as protocols to generate salivary gland cells from iPSCs are still under development 47 , 48 . Conditions for isolation and in vitro culture of adult mouse and human salivary gland mimetics (SGm) were optimized and high-throughput functional assays were developed to assess calcium signaling and secretory cell function relative to native tissue.…”

Section: Introductionmentioning

confidence: 99%

Development of a functional salivary gland tissue chip with potential for high-content drug screening

et al. 2021

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Radiation therapy for head and neck cancers causes salivary gland dysfunction leading to permanent xerostomia. Limited progress in the discovery of new therapeutic strategies is attributed to the lack of in vitro models that mimic salivary gland function and allow high-throughput drug screening. We address this limitation by combining engineered extracellular matrices with microbubble (MB) array technology to develop functional tissue mimetics for mouse and human salivary glands. We demonstrate that mouse and human salivary tissues encapsulated within matrix metalloproteinase-degradable poly(ethylene glycol) hydrogels formed in MB arrays are viable, express key salivary gland markers, and exhibit polarized localization of functional proteins. The salivary gland mimetics (SGm) respond to calcium signaling agonists and secrete salivary proteins. SGm were then used to evaluate radiosensitivity and mitigation of radiation damage using a radioprotective compound. Altogether, SGm exhibit phenotypic and functional parameters of salivary glands, and provide an enabling technology for high-content/throughput drug testing.

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Section: Introductionmentioning

confidence: 99%

Development of a functional salivary gland tissue chip with potential for high-content drug screening

et al. 2021

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“…DPSCs have been used to mimic dental mesenchyme and construct tooth germ organoids (Rosowski et al 2019). In the construction of salivary gland organoids, stem/ progenitor cells with self-organization and self-renewal ability are usually derived from embryonic salivary glands and postnatal ones (Hosseini et al 2019;Sui et al 2020). The SIMS cell line, which includes immortalized adult mouse submandibular salivary gland cells, also can differentiate into unique populations of acinar, myoepithelial, and duct cells under various 3D differentiation conditions (Athwal and Lombaert 2019).…”

Section: Cellsmentioning

confidence: 99%

“…The artificial niche promoted the development of salivary gland organoids, as indicated by the expression of differentiation markers, structure formation, and response to neurotransmitters in vitro. However, the secretory function is decreased due to the absence of continuous stimulation factors (Sui et al 2020). Another approach with fewer exogenous niche factors under 3D culture conditions has also been explored (Shin et al 2018).…”

Section: Asc-derived Sg Organoidsmentioning

confidence: 99%

Oral Organoids: Progress and Challenges

Gao

Liao

et al. 2021

J Dent Res

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Oral organoids are complex 3-dimensional structures that develop from stem cells or organ-specific progenitors through a process of self-organization and re-create architectures and functionalities similar to in vivo organs and tissues in the oral and maxillofacial region. Recently, striking advancements have been made in the construction and application of oral organoids of the tooth, salivary gland, and tongue. Dental epithelial and mesenchymal cells isolated from tooth germs or derived from pluripotent stem cells could generate tooth germ–like organoids by self-organization in a specific culture system. Tooth organoids can also be constructed based on tissue engineering principles by seeding stem cells on a scaffold with the bioregulatory functions of odontogenic differentiation. Two main approaches have been used to construct salivary gland organoids: 1) incubation of salivary gland–derived stem/progenitor cells in a 3-dimensional culture system to form the structure of the gland through mimicking regenerative processes and 2) inducing of pluripotent stem cells to generate embryonic salivary glands by replicating the development process. Taste bud organoids can be generated by embedding isolated circumvallate papilla tissue in Matrigel with a mixture of growth factors, while lingual epithelial organoids have been constructed using lingual stem cells in a suitable culture system containing specific signaling molecules. These oral organoids usually maintain the main functions and characteristic structures of the corresponding organ to a certain extent. Furthermore, using cells isolated from patients, oral organoids could replicate specific diseases such as maxillofacial tumors and tooth dysplasia. Until now, oral organoids have been applied in the study of mechanisms of tooth development, pathology and regeneration of the salivary gland, and precision therapeutics for tongue cancer. These findings strongly demonstrate that the organoid technique is a novel paradigm for the study of the development, pathology, and regeneration of oral and maxillofacial tissue.

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“…The oral cavity contains various tissues, such as teeth, jaws, gingiva, oral mucous, glands, and cartilage, and most of these tissues contain stem cells (Table 1 ). [ 19 ] These stem cells primarily include the tooth-related stem cells DPSCs, SHEDs, GMSCs, PDLSCs, dental follicle progenitor cells (DFPCs), stem cells from the apical papilla (SCAPs), tooth germ stem cells (TGSCs), ABMSCs, and the saliva gland-related stem cells submandibular gland epithelial stem cells (SMGepiSCs) [ 28 ]. Ease of tissue harvest, low population-doubling time, plasticity, multipotential capabilities, and immunomodulatory properties make these cells suitable candidates for various therapeutic strategies [ 20 , 29 ].…”

Section: Oral Tissue Stem Cells and Exosomesmentioning

confidence: 99%

Exosomes from oral tissue stem cells: biological effects and applications

et al. 2020

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As natural nanoparticles, exosomes are a type of extracellular vesicles that are enclosed by a lipid bilayer and contain various cargos, including miRNA, mRNA, DNA and proteins. Exosomes have rapidly gained attention as a highly promising cell-free therapy. Because the cargo of exosomes changes with the changes in parent cells and status, exosomes from different types of cells may exhibit different biological effects. Considering the particularity of oral tissue stem cells, their exosomes were isolated and used to examine their related biological functions and the possibility of replacing stem cells. A variety of exosomes of oral tissue stem cells were studied, and the results revealed many special biological characteristics of these exosomes and their parent cells, especially immunomodulation, osteogenesis, odontogenesis, neuroprotection, nerve regeneration, wound healing, skin regeneration and vascularization. The oral tissue stem cell exosomes may be loaded with drugs or genes and act as tools for tumor treatment. The relevant results showed that exosomes from oral tissue stem cells were potent therapeutic tools. The present review focuses on the biological function and application of oral tissue stem cell-derived exosomes.

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Generation of functional salivary gland tissue from human submandibular gland stem/progenitor cells

Cited by 46 publications

References 37 publications

Development of a functional salivary gland tissue chip with potential for high-content drug screening

Development of a functional salivary gland tissue chip with potential for high-content drug screening

Oral Organoids: Progress and Challenges

Exosomes from oral tissue stem cells: biological effects and applications

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