Flow cytometric isolation of endodermal progenitors from mouse salivary gland differentiate into hepatic and pancreatic lineages

Hisatomi, Yuichiro; Okumura, Kenji; Nakamura, Kimitoshi; Matsumoto, Shirou; Satoh, Ayumi; Nagano, Koji; Yamamoto, Tetsuro; Endo, Fumio

doi:10.1002/hep.20063

Cited by 212 publications

(184 citation statements)

References 28 publications

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“…The blockage results in induced proliferation of duct epithelial cells and expansion of the stem cell population. 10 A recent study has shown that Hh signaling is indeed up-regulated in regenerating SMG following duct ligation. 9 In this model, Hh activation was dependent on and downstream of Wnt, as forced activation of the Wnt pathway in salivary glands activates Hh, expands the stem/ progenitor cell population and promotes proliferation of ductal cells.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study did however suggest that Hh is involved in salivary gland regeneration. 9 When proliferation of salivary gland progenitor/stem cells was induced using the so-called ligation technique, 10 the Wnt signaling pathway and several components of the Hh pathway, including Gli1 and Ptch1, were induced. 9 Hh signaling is also critical for regeneration of several other organs such as stomach and exocrine pancreas.…”

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confidence: 99%

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Targeted Expression of GLI1 in the Salivary Glands Results in an Altered Differentiation Program and Hyperplasia

Fiaschi

Kolterud

Nilsson

et al. 2011

The American Journal of Pathology

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Hedgehog (Hh) signaling is a regulator of salivary gland morphogenesis, but its role in postnatal glands has only recently begun to be addressed. To examine the effects of deregulated Hh signaling in the salivary gland, we expressed the Hh effector protein GLI1, in salivary epithelial cells using both cytokeratin 5 and mouse mammary tumor virus (MMTV) transgenic systems. Ectopic pathway activation resulted in restrained acinar differentiation, formation of cystic lesions, and prominent appearance of ductal structures. Moreover, induced expression of GLI1 aids the formation of hyperplastic lesions, which closely resemble GLI1-induced changes in murine skin and mammary glands, suggesting that GLI1 targets cells with similar characteristics in different tissues. Furthermore, GLI1-expressing salivary epithelial cells are actively dividing, and GLI1-induced lesions are proliferative, an incident accompanied by enhanced expression of the Hh target genes, cyclin D1, and Snail. GLI1-induced salivary lesions regress after transgene withdrawal and become histologically normalized. Taken together, our data reveal the ability of GLI1 to modulate salivary acinar differentiation and to promote proliferation of ductal epithelial cells.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Targeted Expression of GLI1 in the Salivary Glands Results in an Altered Differentiation Program and Hyperplasia

Fiaschi

Kolterud

Nilsson

et al. 2011

The American Journal of Pathology

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“…To determine the ability of the collagen gel culture to induce an endodermal phenotype, we cultured mouse ES cells at a seeding density of 5,000 cells per cm 2 on fibronectin-coated collagen gels, in the presence of 10% serum. By day 10, the cells acquired a characteristic epithelial morphology, with bright cell borders reminiscent of endoderm-like cells [41][42][43] (Fig. 1A).…”

Section: Culture Of Es Cells On Collagen Gels Selectively Induces Endmentioning

confidence: 99%

Activin Alters the Kinetics of Endoderm Induction in Embryonic Stem Cells Cultured on Collagen Gels

et al. 2007

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Embryonic stem cell-derived endoderm is critical for the development of cellular therapies for the treatment of disease such as diabetes, liver cirrhosis, or pulmonary emphysema. Here, we describe a novel approach to induce endoderm from mouse embryonic stem (mES) cells using fibronectin-coated collagen gels. This technique results in a homogeneous endoderm-like cell population, demonstrating endoderm-specific gene and protein expression, which remains committed following in vivo transplantation. In this system, activin, normally an endoderm inducer, caused an 80% decrease in the Foxa2-positive endoderm fraction, whereas follistatin increased the Foxa2-positive endoderm fraction to 78%. Our work suggests that activin delays the induction of endoderm through its transient precursors, the epiblast and mesendoderm. Long-term differentiation displays a twofold reduction in hepatic gene expression and threefold reduction in hepatic protein expression of activintreated cells compared with follistatin-treated cells. Moreover, subcutaneous transplantation of activin-treated cells in a syngeneic mouse generated a heterogeneous teratoma-like mass, suggesting that these were a more primitive population. In contrast, follistatin-treated cells resulted in an encapsulated epithelial-like mass, suggesting that these cells remained committed to the endoderm lineage. In conclusion, we demonstrate a novel technique to induce the direct differentiation of endoderm from mES cells without cell sorting. In addition, our work suggests a new role for activin in induction of the precursors to endoderm and a new endoderm-enrichment technique using follistatin. STEM CELLS 2008;26:474 -484 Disclosure of potential conflicts of interest is found at the end of this article.

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“…[4][5][6] No salivary gland stem cell has been definitively identified as contributing to gland regeneration; however, several duct cell subtypes have been characterized as progenitor cells. [7][8][9][10][11][12] Furthermore, although the direct injection of progenitor cell populations, namely c-Kit + salivary progenitor cells 10,13 or mesenchymal stem cells (MSCs), 14 into irradiated submandibular glands (SMGs) showed some functional improvement, restoration of saliva secretion was incomplete, and highly variable. 13 To reproducibly promote regeneration and functional recovery of irradiated salivary glands, biomaterial-based approaches for cell transplantation have been explored.…”

mentioning

confidence: 99%

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

Shubin

Felong

Graunke

et al. 2015

Tissue Engineering Part A

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More than 40,000 patients are diagnosed with head and neck cancers annually in the United States with the vast majority receiving radiation therapy. Salivary glands are irreparably damaged by radiation therapy resulting in xerostomia, which severely affects patient quality of life. Cell-based therapies have shown some promise in mouse models of radiation-induced xerostomia, but they suffer from insufficient and inconsistent gland regeneration and accompanying secretory function. To aid in the development of regenerative therapies, poly(ethylene glycol) hydrogels were investigated for the encapsulation of primary submandibular gland (SMG) cells for tissue engineering applications. Different methods of hydrogel formation and cell preparation were examined to identify cytocompatible encapsulation conditions for SMG cells. Cell viability was much higher after thiol-ene polymerizations compared with conventional methacrylate polymerizations due to reduced membrane peroxidation and intracellular reactive oxygen species formation. In addition, the formation of multicellular microspheres before encapsulation maximized cell-cell contacts and increased viability of SMG cells over 14-day culture periods. Thiol-ene hydrogel-encapsulated microspheres also promoted SMG proliferation. Lineage tracing was employed to determine the cellular composition of hydrogel-encapsulated microspheres using markers for acinar (Mist1) and duct (Keratin5) cells. Our findings indicate that both acinar and duct cell phenotypes are present throughout the 14 day culture period. However, the acinar:duct cell ratios are reduced over time, likely due to duct cell proliferation. Altogether, permissive encapsulation methods for primary SMG cells have been identified that promote cell viability, proliferation, and maintenance of differentiated salivary gland cell phenotypes, which allows for translation of this approach for salivary gland tissue engineering applications.

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Flow cytometric isolation of endodermal progenitors from mouse salivary gland differentiate into hepatic and pancreatic lineages

Cited by 212 publications

References 28 publications

Targeted Expression of GLI1 in the Salivary Glands Results in an Altered Differentiation Program and Hyperplasia

Targeted Expression of GLI1 in the Salivary Glands Results in an Altered Differentiation Program and Hyperplasia

Activin Alters the Kinetics of Endoderm Induction in Embryonic Stem Cells Cultured on Collagen Gels

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

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