A morphogenetic concept of salivary duct regeneration and metaplasia

Ihrler, Stephan; Zietz, Christian; Sendelhofert, Andrea; Lang, Stephan; Blasenbreu-Vogt, Sabine; Löhrs, U.

doi:10.1007/s004280100537

Cited by 71 publications

(75 citation statements)

References 29 publications

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“…There are also a number of reports mentioning that epithelial stem cells of the salivary gland duct are present in intercalated ducts 36,37) and that they are present in the duct-like structures of atrophied salivary glands 7,38) . In addition, differentiated cells are reported to participate in regeneration 38,39) . In the present study, we found PSCA in the intercalated ducts of normal submandibular glands and c-Kit in the duct-like structures of atrophied salivary glands.…”

Section: Discussionmentioning

confidence: 99%

Regenerative Capacity of Atrophic Submandibular Gland by Duct Ligation in Mice

Akadomari

Tanaka

Mataga

2016

J. Hard Tissue Biology.

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Function degeneracy of the salivary gland leads to reduced protection against infection and reduced physiological function of the oral cavity, considerably diminishing the patient's quality of life. However, no method of treatment has yet been established to recover the secretory capacity of the salivary gland reduced by the degeneration or disappearance of the gland tissue. Ongoing salivary gland regeneration experiments using cell transplantation aim to introduce clinical regenerative treatment for the salivary gland. Because it is essential to understand the self-regenerative capacity that remains in the recipient's salivary gland, it is essential to search for optimal conditions for transplantation and establish a salivary gland atrophy model. In this context, we performed duct ligation of the submandibular gland in groups of mice for 7-, 14-, and 21-day ligation periods, compared immunohistochemical staining using acinar cell and stem cell markers, detected apoptosis using TUNEL staining, and analyzed gene expression using RT-PCR to search for the expression of factors related to regenerative capacity that remain in the atrophic salivary gland. All 3 periods of ligation led to remarkable atrophy/disappearance of acinar cells and the dominant presence of duct-like structures. These structures expressed stem cell markers most intensively after 14 days of ligation, and double immunostaining revealed the expressions of PSCA and c-Kit that coincided with them. AQP5 expression was detected in acinar cells and the apical membrane of the intercalated ducts in the normal submandibular gland and was also detected after 21 days of ligation in the remnant acinar cells and intercalated ducts. Conversely, the number of TUNELpositive apoptotic cells in the atrophic salivary gland was highest after 7 days of ligation. These results showed that the duct-like structures that exist after ligation expressed stem cell markers and AQP5, indicating the presence of a mechanism related to the regeneration of salivary gland tissue.

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Section: Discussionmentioning

confidence: 99%

Regenerative Capacity of Atrophic Submandibular Gland by Duct Ligation in Mice

Akadomari

Tanaka

Mataga

2016

J. Hard Tissue Biology.

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“…Although K14 expression in mature gland is restricted to MECs and the basal layer of excretory ducts [27,28], during embryonic development, K14 is expressed in a multipotent progenitor population [10] (Supplementary Fig. S1A; Supplementary Data are available online at www.liebertpub.com/scd).…”

Section: Uniform Loss Of H2bgfp Label From K14-expressing Ductal Cellsmentioning

confidence: 99%

Analysis of Histone H2BGFP Retention in Mouse Submandibular Gland Reveals Actively Dividing Stem Cell Populations

Kwak

Ghazizadeh

2015

Stem Cells and Development

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The purpose of this study was to use histone 2B-green fluorescent protein (H2BGFP) pulse-chase experiments to provide a broad view of population dynamics in salivary gland and to identify the quiescent stem cells that had previously been suggested to reside in the gland. Two transgenic mouse models in which inducible H2BGFP expression was regulated either by keratin (K)14 promoter or by a ubiquitous promoter were generated. The level of fluorescent label in the submandibular gland induced by a pulse of H2BGFP expression was monitored over a period of 18 weeks of chase. Efficient targeting of H2BGFP label to the relatively undifferentiated ductal cells by K14 promoter did not identify a quiescent population of stem cells. Ubiquitous targeting of all ductal cells identified label-retaining cells but these cells were mapped to the more differentiating ductal compartments. Furthermore, they did not display the major characteristics of quiescent stem cells including the undifferentiated phenotype, mobilization in response to injury, and the clonogenicity in culture. Quantitative assessment of H2BGFP loss in various ductal compartments and short-term lineage tracing of K14 + ductal cells were consistent with the presence of actively dividing pools of stem/progenitor cells in the intercalated ducts and the basal layer of excretory ducts functioning independently during homeostasis.

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“…The existence of stem cells in salivary glands has been postulated, and newly formed acinar cells are believed to differentiate from the rapidly proliferating intercalated duct cells (14,34). On the other hand, other studies have shown that acinar cells can proliferate and are potential progenitor cells, although they are highly differentiated (24,52).…”

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confidence: 99%