scholarly journals Capability of Tissue Stem Cells to Organize into Salivary Rudiments

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Kenji Okumura ◽  
Masanori Shinohara ◽  
Fumio Endo
Keyword(s):  
Stem Cells ◽  
Salivary Gland ◽  
Salivary Glands ◽  
Progenitor Cells ◽  
Duct Cell ◽  
Branching Morphogenesis ◽  
Embryonic Cells ◽  
Gland Development ◽  
Salivary Epithelia ◽  
Pseudoglandular Stage

Branching morphogenesis (BrM), an essential step for salivary gland development, requires epithelial-mesenchymal interactions. BrM is impaired when the surrounding mesenchyme is detached from the salivary epithelium during the pseudoglandular stage. It is believed that the salivary mesenchyme is indispensable for BrM, however, an extracellular matrix gel with exogenous EGF can be used as a substitute for the mesenchyme during BrM in the developing salivary epithelium. Stem/progenitor cells isolated from salivary glands in humans and rodents can be classified as mesenchymal stem cell-like, bone-marrow-derived, duct cell-like, and embryonic epithelium-like cells. Salivary-gland-derived progenitor (SGP) cells isolated from duct-ligated rats, mice, and swine submandibular glands share similar characteristics, including intracellular laminin andα6β1-integrin expression, similar to the embryonic salivary epithelia during the pseudoglandular stage. Progenitor cells also isolated from human salivary glands (human SGP cells) having the same characteristics differentiate into hepatocyte-like cells when transplanted into the liver. Similar to the dissociated embryonic salivary epithelium, human SGP cells aggregate to self-organize into branching organ-like structures on Matrigel plus exogenous EGF. These results suggest the possibility that tissue stem cells organize rudiment-like structures, and the embryonic cells that organize into whole tissues during development are preserved even in adult tissues.

Mesenchymal control over elongating and branching morphogenesis in salivary gland development

Development ◽  
1981 ◽  
Vol 66 (1) ◽  
pp. 209-221
Author(s):  
Hiroyuki Nogawa ◽  
Takeo Mizuno
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Submaxillary Gland ◽  
Branching Morphogenesis ◽  
Mouse Submaxillary Gland ◽  
Gland Development

Recombination of the epithelium and mesenchyme between quail anterior submaxillary gland (elongating type) and quail anterior lingual or mouse submaxillary gland (branching type) was effected in vitro to clarify whether the elongating morphogenesis was directed by the epithelial or the mesenchymal component. Quail anterior submaxillary epithelium recombined with quail anterior lingual or mouse submaxillary mesenchyme came to branch. Conversely, quail anterior lingual or 12-day mouse submaxillary epithelium recombined with quail anterior submaxillary mesenchyme came to elongate, though the mesenchyme was less effective with 13-day mouse submaxillary epithelium. These results suggest that the elongating or branching morphogenesis of quail salivary glands is controlled by the mesenchyme.

Dual Sympathetic Input into Developing Salivary Glands

2019 ◽  
Vol 98 (10) ◽  
pp. 1122-1130 ◽  
Author(s):  
T.H.N. Teshima ◽  
A.S. Tucker ◽  
S.V. Lourenço
Keyword(s):  
Salivary Gland ◽  
Superior Cervical Ganglion ◽  
Time Course ◽  
Sympathetic Nerves ◽  
Branching Morphogenesis ◽  
Developmental Time ◽  
Explant Culture ◽  
Early Stages ◽  
Cervical Ganglion ◽  
Gland Development

Neuronal signaling is known to be required for salivary gland development, with parasympathetic nerves interacting with the surrounding tissues from early stages to maintain a progenitor cell population and control morphogenesis. In contrast, postganglionic sympathetic nerves arrive late in salivary gland development to perform a secretory function; however, no previous report has shown their role during development. Here, we show that a subset of neuronal cells within the parasympathetic submandibular ganglion (PSG) express the catecholaminergic marker tyrosine hydroxylase (TH) in developing murine and human submandibular glands. This sympathetic phenotype coincided with the expression of transcription factor Hand2 within the PSG from the bud stage (E12.5) of mouse embryonic salivary gland development. Hand2 was previously associated with the decision of neural crest cells to become sympathetic in other systems, suggesting a role in controlling neuronal fate in the salivary gland. The PSG therefore provides a population of TH-expressing neurons prior to the arrival of the postganglionic sympathetic axons from the superior cervical ganglion at E15.5. In culture, in the absence of nerves from the superior cervical ganglion, these PSG-derived TH neurons were clearly evident forming a network around the gland. Chemical ablation of dopamine receptors in explant culture with the neurotoxin 6-hydroxydopamine at early stages of gland development resulted in specific loss of the TH-positive neurons from the PSG, and subsequent branching was inhibited. Taken altogether, these results highlight for the first time the detailed developmental time course of TH-expressing neurons during murine salivary gland development and suggest a role for these neurons in branching morphogenesis.

scholarly journals In vitro induction and in vivo engraftment of lung bud tip progenitor cells derived from human pluripotent stem cells

2017 ◽  
Author(s):  
Alyssa J. Miller ◽  
David R. Hill ◽  
Melinda S. Nagy ◽  
Yoshiro Aoki ◽  
Briana R. Dye ◽  
...  
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Fetal Lung ◽  
Branching Morphogenesis ◽  
Human Pluripotent Stem Cells ◽  
3 Dimensional ◽  
Lung Epithelial ◽  
Human Fetal Lung

SummaryThe bud tip epithelium of the branching mouse and human lung contains multipotent progenitors that are able to self-renew and give rise to all mature lung epithelial cell types. The current study aimed to understand the developmental signaling cues that regulate bud tip progenitor cells in the human fetal lung, which are present during branching morphogenesis, and to use this information to induce a bud tip progenitor-like population from human pluripotent stem cells (hPSCs) in vitro. We identified that FGF7, CHIR-99021 and RA maintained isolated human fetal lung epithelial bud tip progenitor cells in an undifferentiated state in vitro, and led to the induction of a 3-dimensional lung-like epithelium from hPSCs. 3-dimensional hPSC-derived lung tissue was initially patterned, with airway-like interior domains and bud tip-like progenitor domains at the periphery. Epithelial bud tip-like domains could be isolated, expanded and maintained as a nearly homogeneous population by serial passaging. Comparisons between human fetal lung epithelial bud tip cells and hPSC-derived bud tip-like cells were carried out using immunostaining, in situ hybridization and transcriptome-wide analysis, and revealed that in vitro derived tissue was highly similar to native lung. hPSC-derived epithelial bud tip-like structures survived in vitro for over 16 weeks, could be easily frozen and thawed and maintained multi-lineage potential. Furthermore, hPSC-derived epithelial bud tip progenitors successfully engrafted in the proximal airways of injured immunocompromised NSG mouse lungs, where they persisted for up to 6 weeks and gave rise to several lung epithelial lineages.

scholarly journals Neonatal Wnt-dependent Lgr5 positive stem cells are essential for uterine gland development

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ryo Seishima ◽  
Carly Leung ◽  
Swathi Yada ◽  
Katzrin Bte Ahmed Murad ◽  
Liang Thing Tan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Reproductive Tract ◽  
Ex Vivo ◽  
Lineage Tracing ◽  
Major Advance ◽  
Uterine Gland ◽  
And Function ◽  
Gland Development

AbstractWnt signaling is critical for directing epithelial gland development within the uterine lining to ensure successful gestation in adults. Wnt-dependent, Lgr5-expressing stem/progenitor cells are essential for the development of glandular epithelia in the intestine and stomach, but their existence in the developing reproductive tract has not been investigated. Here, we employ Lgr5-2A-EGFP/CreERT2/DTR mouse models to identify Lgr5-expressing cells in the developing uterus and to evaluate their stem cell identity and function. Lgr5 is broadly expressed in the uterine epithelium during embryogenesis, but becomes largely restricted to the tips of developing glands after birth. In-vivo lineage tracing/ablation/organoid culture assays identify these gland-resident Lgr5high cells as Wnt-dependent stem cells responsible for uterine gland development. Adjacent Lgr5neg epithelial cells within the neonatal glands function as essential niche components to support the function of Lgr5high stem cells ex-vivo. These findings constitute a major advance in our understanding of uterine development and lay the foundations for investigating potential contributions of Lgr5+ stem/progenitor cells to uterine disorders.

scholarly journals Fgf10 and Sox9 are essential for the establishment of distal progenitor cells during mouse salivary gland development

Development ◽  
2017 ◽  
Vol 144 (12) ◽  
pp. 2294-2305 ◽  
Author(s):  
Lemonia Chatzeli ◽  
Marcia Gaete ◽  
Abigail S. Tucker
Keyword(s):  
Salivary Gland ◽  
Progenitor Cells ◽  
Gland Development

scholarly journals Human salivary gland stem cells ameliorate hyposalivation of radiation-damaged rat salivary glands

2013 ◽  
Vol 45 (11) ◽  
pp. e58-e58 ◽  
Author(s):  
Jaemin Jeong ◽  
Hyunjung Baek ◽  
Yoon-Ju Kim ◽  
Youngwook Choi ◽  
Heekyung Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Salivary Gland ◽  
Salivary Glands ◽  
Human Salivary Gland ◽  
Rat Salivary Glands

Exosomes Derived from Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSC) Protect Submandibular Glands in Diabetic Rats

2021 ◽  
Vol 11 (11) ◽  
pp. 2168-2173
Author(s):  
Cong Zhang ◽  
Xiaohong Zhang ◽  
Min Zhang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Salivary Gland ◽  
Salivary Glands ◽  
Serum Amylase ◽  
Diabetic Rats ◽  
Submandibular Salivary Gland ◽  
Amylase Level ◽  
Group I

Our study assess whether exosomes derived from bone marrow mesenchymal stem cells (BM-MSC) ameliorates diabetic salivary gland complications. 10 SD rats were assigned into diabetes group I and exosome treatment group II. Diabetic rats were induced by streptozotocin (STZ) and injected with DMSO or exosomes through tail vein followed by collection of submandibular salivary gland samples for histological analysis and TGFβ, Smad2 and Smad3 level by PCR, saliva IgA and serum amylase level. Compared with control mice, exosome treatment mice showed less fibrosis of the submandibular salivary glands and duct components with a more complete structure. Exosome treatment inhibited TGFβ, Smad2 and Smad3 level to reduce diabetic salivary gland complications, effectively decreased blood sugar level, improved salivary glands function with significantly reduced serum amylase and salivary IgA levels. In conclusion, BM-MSC-derived exosomes may be a new therapeutic strategy for treating diabetic salivary gland complications.

Bone Marrow-Derived Stem Cells Reduce Radiation-Induced Damage to Salivary Glands.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1194-1194
Author(s):  
Pieter K. Wierenga ◽  
Isabelle Lombaert ◽  
Willy Visser ◽  
Harm H. Kampinga ◽  
Gerald de Haan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Salivary Gland ◽  
Salivary Glands ◽  
Laser Fluorescence ◽  
Egfp Expression ◽  
Confocal Laser ◽  
Optimal Time ◽  
Similar Amount ◽  
Radiation Induced

Abstract The salivary glands are often included in the field of irradiation during radiotherapy of head and neck cancer. This can result in severe side-effects that reduces the quality of life of the patient and may even limit the treatment dose. Late damage to the salivary glands is mainly caused by exhaustion of the tissue specific stem cells. Post-irradiation replacement of salivary gland stem cells with donor stem cells may ameliorate radiation-induced complications. Bone marrow-derived stem cells (BMSC) have been shown to be multipotent and thereby able to engraft in many tissues after injury. In this study, we assessed the potential of BMSC to reduce irradiation-induced salivary gland damage. C57BL/6 mice were transplanted with bone marrow from eGFP transgenic animals. After two months the salivary glands of these chimeric mice were locally irradiated with 15 Gy. BMSC were mobilized 10, 30 and/or 60 days after irradiation by s.c. injection of rHu-PEG-G-CSF. Saliva secretion (μl/15 minutes) was measured up to 90 days after irradiation by pilocarpine induction. Hereafter, the glands were extirpated and examined for eGFP-expression. From every individual animal one parotid and one submandibular gland was used to prepare single cell suspensions in order to detect eGFP-positve cells by flow cytometry. The other parotid and submandibular glands were analyzed using confocal laser fluorescence scanning microscopy and light microscopy. G-CSF treatment yielded in an increase of saliva flow for all time points. The optimal time-point for mobilization, however, was 30 days after irradiation as is demonstrated by an improvement of salivary flow from 5 to 30% when compared to radiation alone. FACS analysis showed that up to 10% of the isolated cells were eGFP-positive. Microscopic analysis revealed a similar amount of positive cells and an improved morphology. Immuno-histochemistry using anti-SM-actin antibodies showed the close vicinity of actin and eGFP within the cells, demonstrating the occurence of BMSC derived myoepithelial cells in irradiated salivary glands. Furthermore, using cell-type specific antibodies, the meyoepethilial nature of the eGFP positive was revealed. In conclusion, the results show that BMSC home to severely damaged salivary glands after mobilization. Hence, BMSC mobilization could become a promising modality to ameliorate radiation-induced complications in salivary glands after radiotherapy.

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