Functional Salivary Gland Regeneration by Organ Replacement Therapy

Ogawa, Miho; Tsuji, Takashi

doi:10.1007/978-3-319-43513-8_10

Cited by 4 publications

(2 citation statements)

References 69 publications

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“…While most current treatments for salivary gland dysfunction target expansion of residual salivary acinar cells to repair damaged tissue, regenerative therapy with stem cells is a novel and promising therapeutic approach to replace damaged salivary glands (Carpenter and Cotroneo, 2010;Lombaert et al, 2017;Ogawa and Tsuji, 2017). Several studies have identified and characterized subsets of endogenous salivary progenitor cells that can be exploited to promote tissue regeneration (Lombaert et al, 2008;Chibly et al, 2014Chibly et al, , 2018Pringle et al, 2016;Emmerson et al, 2018;Weng et al, 2018).…”

Section: P2 Receptors In Salivary Gland Regenerationmentioning

confidence: 99%

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

et al. 2020

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Although often overlooked in our daily lives, saliva performs a host of necessary physiological functions, including lubricating and protecting the oral cavity, facilitating taste sensation and digestion and maintaining tooth enamel. Therefore, salivary gland dysfunction and hyposalivation, often resulting from pathogenesis of the autoimmune disease Sjögren's syndrome or from radiotherapy of the head and neck region during cancer treatment, severely reduce the quality of life of afflicted patients and can lead to dental caries, periodontitis, digestive disorders, loss of taste and difficulty speaking. Since their initial discovery in the 1970s, P2 purinergic receptors for extracellular nucleotides, including ATP-gated ion channel P2X and G protein-coupled P2Y receptors, have been shown to mediate physiological processes in numerous tissues, including the salivary glands where P2 receptors represent a link between canonical and non-canonical saliva secretion. Additionally, extracellular nucleotides released during periods of cellular stress and inflammation act as a tissue alarmin to coordinate immunological and tissue repair responses through P2 receptor activation. Accordingly, P2 receptors have gained widespread clinical interest with agonists and antagonists either currently undergoing clinical trials or already approved for human use. Here, we review the contributions of P2 receptors to salivary gland function and describe their role in salivary gland dysfunction. We further consider their potential as therapeutic targets to promote physiological saliva flow, prevent salivary gland inflammation and enhance tissue regeneration.

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Section: P2 Receptors In Salivary Gland Regenerationmentioning

confidence: 99%

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

et al. 2020

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“…In addition, we also found α-SMA positive cells at the outer layer of SG placodes, which are expressed in SGs through development and maturation (Additional file 1 : Fig. S3A-B) [ 29 ]. RNA-seq was performed to further characterize the PSC-derived SG placodes.…”

Section: Resultsmentioning

confidence: 99%

Retinoic acid and FGF10 promote the differentiation of pluripotent stem cells into salivary gland placodes

et al. 2022

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Background Salivary glands produce saliva that play essential roles in digestion and oral health. Derivation of salivary gland organoids from pluripotent stem cells (PSCs) provides a powerful platform to model the organogenesis processes during development. A few studies attempted to differentiate PSCs into salivary gland organoids. However, none of them could recapitulate the morphogenesis of the embryonic salivary glands, and most of the protocols involved complicated manufacturing processes. Methods To generate PSC-derived salivary gland placodes, the mouse embryonic stem cells were first differentiated into oral ectoderm by treatment with BMP4 on day 3. Retinoic acid and bFGF were then applied to the cultures from day 4 to day 6, followed by a 4-day treatment of FGF10. The PSC-derived salivary gland placodes on day 10 were transplanted to kidney capsules to determine the regenerative potential. Quantitative reverse transcriptase–polymerase chain reaction, immunofluorescence, and RNA-sequencing were performed to identify the PSC-derived SG placodes. Results We showed that step-wise treatment of retinoic acid and FGF10 promoted the differentiation of PSCs into salivary gland placodes, which can recapitulate the early morphogenetic events of their fetal counterparts, including the thickening, invagination, and then formed initial buds. The PSC-derived salivary gland placodes also differentiated into developing duct structures and could develop to striated and excretory ducts when transplanted in vivo. Conclusions The present study provided an easy and safe method to generate salivary gland placodes from PSCs, which offered possibilities for studying salivary gland development in vitro and developing new cell therapies.

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Derivation of Human Salivary Epithelial Progenitors from Pluripotent Stem Cells via Activation of RA and Wnt Signaling

Zhang

Sui

Zhang

et al. 2022

Stem Cell Rev and Rep

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Functional Salivary Gland Regeneration by Organ Replacement Therapy

Cited by 4 publications

References 69 publications

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

Retinoic acid and FGF10 promote the differentiation of pluripotent stem cells into salivary gland placodes

Derivation of Human Salivary Epithelial Progenitors from Pluripotent Stem Cells via Activation of RA and Wnt Signaling

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