Functional transplantation of salivary gland cells differentiated from mouse early ES cells in vitro

Kawakami, Miyuki; Ishikawa, Hiroshi; Tachibana, Toshiaki; Tanaka, Akira; Mataga, Izumi

doi:10.1007/s13577-013-0061-z

Cited by 37 publications

(31 citation statements)

References 23 publications

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“…Studies of residual salivary gland function and regeneration function in atrophied salivary glands expression of the acinar cell markers -amylase [24][25][26] and AQP5 23,[26][27][28] , and stem-cell markers such as c-kit [19][20][21][22][23] are investigated. However, all of these results are from short-term ligation.…”

Section: Discussionmentioning

confidence: 99%

Chronic Changes in the Atrophied Submandibular Gland after Long-term Ligation of the Main Excretory Duct in Mice

Murayama

Kawakami

Tanaka

2017

J. Hard Tissue Biology.

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To examine the pathology of salivary glands that have undergone atrophy or hypofunction due to old age or disease, the duct ligation model is used. This model has been used in studies on the course of glandular parenchyma atrophy and the potential for repair and regeneration. However, the period of ligation was short in most of these studies, and none have examined long-term progress. Therefore, we investigated long-term ligation of the submandibular gland in mice and examined the chronic changes in atrophied salivary glands. The ligation periods were 1, 2 and 3 months, and atrophied salivary glands were resected after each period. Resected glands were examined by histology, immunohistochemistry, RT-PCR, and transmission electron microscopy. Histologically, disappearance of acinar cells and increases in duct-like structures were observed over time in atrophied salivary glands, resulting from long-term submandibular gland main excretory duct ligation. Acinar cell markers (-amylase, aquaporin 5) showed marked weakness in expression after ligation, but expression was still observed after 3 months of ligation. Stem cell markers (c-kit, Sca-1) showed greater expression at 1 month of ligation, compared with controls, but expression subsequently decreased with time. Expression of the precursor cell marker cytokeratin 5 was retained throughout long-term ligation. Atrophied salivary gland tissue resulting from long-term ligation showed increases in specific duct-like structures over time, and the expression of stem cell markers and progenitor cell markers in the area of these structures suggests that the repair capability remained intact.

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Section: Discussionmentioning

confidence: 99%

Chronic Changes in the Atrophied Submandibular Gland after Long-term Ligation of the Main Excretory Duct in Mice

Murayama

Kawakami

Tanaka

2017

J. Hard Tissue Biology.

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“…There are currently no therapeutic strategies for recovering gland tissue or diminished or lost salivary secretion function. Experiments in cell transplantation are currently underway with the aim of introducing clinical therapy for salivary gland regeneration 5) . It is essential to have a firm understanding of the self-renewal capability remaining in the salivary gland of the recipient, which will be the substrate onto which cells are transplanted; therefore, there is a pressing need to investigate the optimal conditions for transplantation and to establish a model of salivary gland atrophy.…”

Section: Introductionmentioning

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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“…These reports include several types of stem cells such as bone marrow- (BM-) derived cells [63, 64], BM-derived mesenchymal stem cells (MSCs) [14, 52], human adipose-derived MSCs [53, 54], SG-derived MSC-like cells [55], amniotic cells [56, 57], embryonic stem cells (ESC) [58], and induced-pluripotent stem cells (iPSC) [59]. …”

Section: Nonsalivary Gland Cells and Their Secretomementioning

confidence: 99%

“…Other pluripotent cell types such as ESC and iPSC have recently been investigated as new cell sources to generate mature salivary gland cells [58, 59]. A study with mouse ESCs cocultured with human SG-derived fibroblast has provided (to ESCs) the cues to express SG-specific markers and to reconstitute SG structures; however, it is still unclear whether SG function can be restored [58].…”

Section: Nonsalivary Gland Cells and Their Secretomementioning

confidence: 99%

Three‐Dimensional Bioprinting Nanotechnologies towards Clinical Application of Stem Cells and Their Secretome in Salivary Gland Regeneration

Ferreira

Rungarunlert

Urkasemsin

et al. 2016

Stem Cells International

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Salivary gland (SG) functional damage and severe dry mouth (or xerostomia) are commonly observed in a wide range of medical conditions from autoimmune to metabolic disorders as well as after radiotherapy to treat specific head and neck cancers. No effective therapy has been developed to completely restore the SG functional damage on the long-term and reverse the poor quality of life of xerostomia patients. Cell- and secretome-based strategies are currently being tested in vitro and in vivo for the repair and/or regeneration of the damaged SG using (1) epithelial SG stem/progenitor cells from salispheres or explant cultures as well as (2) nonepithelial stem cell types and/or their bioactive secretome. These strategies will be the focus of our review. Herein, innovative 3D bioprinting nanotechnologies for the generation of organotypic cultures and SG organoids/mini-glands will also be discussed. These bioprinting technologies will allow researchers to analyze the secretome components and extracellular matrix production, as well as their biofunctional effects in 3D mini-glands ex vivo. Improving our understanding of the SG secretome is critical to develop effective secretome-based therapies towards the regeneration and/or repair of all SG compartments for proper restoration of saliva secretion and flow into the oral cavity.

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Functional transplantation of salivary gland cells differentiated from mouse early ES cells in vitro

Cited by 37 publications

References 23 publications

Chronic Changes in the Atrophied Submandibular Gland after Long-term Ligation of the Main Excretory Duct in Mice

Chronic Changes in the Atrophied Submandibular Gland after Long-term Ligation of the Main Excretory Duct in Mice

Regenerative Capacity of Atrophic Submandibular Gland by Duct Ligation in Mice

Three‐Dimensional Bioprinting Nanotechnologies towards Clinical Application of Stem Cells and Their Secretome in Salivary Gland Regeneration

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