scholarly journals Organoid Models for Salivary Gland Biology and Regenerative Medicine

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Chen Zhao ◽  
Cuida Meng ◽  
Na Cui ◽  
Jichao Sha ◽  
Liwei Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Salivary Gland ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Salivary Gland Tissue ◽  
Gland Tissue ◽  
Gland Function ◽  
Key Aspects ◽  
Complex Architecture

The salivary gland is composed of an elegant epithelial network that secrets saliva and maintains oral homeostasis. While cell lines and animal models furthered our understanding of salivary gland biology, they cannot replicate key aspects of the human salivary gland tissue, particularly the complex architecture and microenvironmental features that dictate salivary gland function. Organoid cultures provide an alternative system to recapitulate salivary gland tissue in vitro, and salivary gland organoids have been generated from pluripotent stem cells and adult stem/progenitor cells. In this review, we describe salivary gland organoids, the advances and limitations, and the promising potential for regenerative medicine.

Hyperglycemia Induces Generation of Reactive Oxygen Species and Accelerates Apoptotic Cell Death in Salivary Gland Cells

Pathobiology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Naoyuki Matsumoto ◽  
Daisuke Omagari ◽  
Ryoko Ushikoshi-Nakayama ◽  
Tomoe Yamazaki ◽  
Hiroko Inoue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Salivary Gland ◽  
Tissue Injury ◽  
Ros Production ◽  
Oxygen Species ◽  
Saliva Secretion ◽  
Salivary Gland Tissue ◽  
Gland Tissue

<b><i>Introduction:</i></b> Type-2 diabetes mellitus (T2DM) is associated with several systemic vascular symptoms and xerostomia. It is considered that hyperglycemia-induced polyuria and dehydration cause decreased body-water volume, leading to decreased saliva secretion and, ultimately, xerostomia. In T2DM, increased production of reactive oxygen species (ROS) causes tissue damage to vascular endothelial cells as well as epithelial tissue, including pancreas and cornea. Hence, a similar phenomenon may occur in other tissues and glands in a hyperglycemic environment. <b><i>Methods:</i></b> Salivary gland tissue injury was examined, using T2DM model mouse (db/db). Transferase‐mediated dUTP nick‐end labeling (TUNEL) was conducted to evaluate tissue injury. The levels of malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine, Bax/Bcl-2 ratio were measured as indicator of oxidative stress. Moreover, in vitro ROS production and cell injury was evaluated by mouse salivary gland-derived normal cells under high-glucose condition culture. <b><i>Results:</i></b> In vivo and in vitro analysis showed a higher percentage of TUNEL-positive cells and higher levels of MDA and 8-hydroxy-2′-deoxyguanosine in salivary gland tissue of db/db mice. This suggests damage of saliva secretion-associated lipids and DNA by hyperglycemic-induced oxidative stress. To analyze the mechanism by which hyperglycemia promotes ROS production, mouse salivary gland-derived cells were isolated. The cell culture with high-glucose medium enhanced ROS production and promotes apoptotic and necrotic cell death. <b><i>Conclusion:</i></b> These findings suggest a novel mechanism whereby hyperglycemic-induced ROS production promotes salivary gland injury, resulting in hyposalivation.

scholarly journals Induction of functional hypothalamus and pituitary tissues from pluripotent stem cells for regenerative medicine

2020 ◽  
Author(s):  
Mayuko Kano ◽  
Hidetaka Suga ◽  
Hiroshi Arima
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Hormone Replacement ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Hormone Deficiency ◽  
Adrenal Crisis ◽  
Mouse Escs

Abstract The hypothalamus and pituitary have been identified to play essential roles in maintaining homeostasis. Various diseases can disrupt the functions of these systems, which can often result in serious lifelong symptoms. The current treatment for hypopituitarism involves hormone replacement therapy. However, exogenous drug administration cannot mimic the physiological changes that are a result of hormone requirements. Therefore, patients are at a high risk of severe hormone deficiency, including adrenal crisis. Pluripotent stem cells (PSCs) self-proliferate and differentiate into all types of cells. The generation of endocrine tissues from PSCs has been considered as another new treatment for hypopituitarism. Our colleagues established a three-dimensional culture method for embryonic stem cells (ESCs). In this culture, the ESC-derived aggregates exhibit self-organization and spontaneous formation of highly ordered patterning. Recent results have shown that strict removal of exogenous patterning factors during early differentiation efficiently induces rostral hypothalamic progenitors from mouse ESCs. These hypothalamic progenitors generate vasopressinergic neurons, which release neuropeptides upon exogenous stimulation. Subsequently, we reported adenohypophysis tissue self-formation in three-dimensional cultures of mouse ESCs. The ESCs were found to differentiate into both non-neural oral ectoderm and hypothalamic neuroectoderm in adjacent layers. Interactions between the two tissues appear to be critically important for in vitro induction of a Rathke's pouch-like developing embryo. Various endocrine cells were differentiated from non-neural ectoderm. The induced corticotrophs efficiently secreted adrenocorticotropic hormone when engrafted in vivo, which rescued hypopituitary hosts. For future regenerative medicine, generation of hypothalamic and pituitary tissues from human PSCs is necessary. We and other groups succeeded in establishing a differentiation method with the use of human PSCs. Researchers could use these methods for models of human diseases to elucidate disease pathology or screen potential therapeutics.

scholarly journals Induced Pluripotent Stem Cells as Vasculature Forming Entities

2019 ◽  
Vol 8 (11) ◽  
pp. 1782 ◽  
Author(s):  
Antonio Palladino ◽  
Isabella Mavaro ◽  
Carmela Pizzoleo ◽  
Elena De Felice ◽  
Carla Lucini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Tissue Growth ◽  
Safety Issues ◽  
Induced Pluripotent

Tissue engineering (TE) pursues the ambitious goal to heal damaged tissues. One of the most successful TE approaches relies on the use of scaffolds specifically designed and fabricated to promote tissue growth. During regeneration the guidance of biological events may be essential to sustain vasculature neoformation inside the engineered scaffold. In this context, one of the most effective strategies includes the incorporation of vasculature forming cells, namely endothelial cells (EC), into engineered constructs. However, the most common EC sources currently available, intended as primary cells, are affected by several limitations that make them inappropriate to personalized medicine. Human induced Pluripotent Stem Cells (hiPSC), since the time of their discovery, represent an unprecedented opportunity for regenerative medicine applications. Unfortunately, human induced Pluripotent Stem Cells-Endothelial Cells (hiPSC-ECs) still display significant safety issues. In this work, we reviewed the most effective protocols to induce pluripotency, to generate cells displaying the endothelial phenotype and to perform an efficient and safe cell selection. We also provide noteworthy examples of both in vitro and in vivo applications of hiPSC-ECs in order to highlight their ability to form functional blood vessels. In conclusion, we propose hiPSC-ECs as the preferred source of endothelial cells currently available in the field of personalized regenerative medicine.

Hepatic differentiation of pluripotent stem cells

2009 ◽  
Vol 390 (10) ◽  
Author(s):  
Komal Loya ◽  
Reto Eggenschwiler ◽  
Kinarm Ko ◽  
Malte Sgodda ◽  
Francoise André ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Ethical Issues ◽  
Es Cells ◽  
Embryonic Stem ◽  
Hepatic Differentiation ◽  
Alternative Source ◽  
Organ Specific

Abstract In regenerative medicine pluripotent stem cells are considered to be a valuable self-renewing source for therapeutic cell transplantations, given that a functional organ-specific phenotype can be acquired by in vitro differentiation protocols. Furthermore, derivatives of pluripotent stem cells that mimic fetal progenitor stages could serve as an important tool to analyze organ development with in vitro approaches. Because of ethical issues regarding the generation of human embryonic stem (ES) cells, other sources for pluripotent stem cells are intensively studied. Like in less developed vertebrates, pluripotent stem cells can be generated from the female germline even in mammals, via parthenogenetic activation of oocytes. Recently, testis-derived pluripotent stem cells were derived from the male germline. Therefore, we compared two different hepatic differentiation approaches and analyzed the generation of definitive endoderm progenitor cells and their further maturation into a hepatic phenotype using murine parthenogenetic ES cells, germline-derived pluripotent stem cells, and ES cells. Applying quantitative RT-PCR, both germline-derived pluripotent cell lines show similar differentiation capabilities as normal murine ES cells and can be considered an alternative source for pluripotent stem cells in regenerative medicine.

scholarly journals Genome maintenance in pluripotent stem cells

2014 ◽  
Vol 204 (2) ◽  
pp. 153-163 ◽  
Author(s):  
Uri Weissbein ◽  
Nissim Benvenisty ◽  
Uri Ben-David
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
In Vitro Propagation ◽  
Basic Research ◽  
Culture Conditions ◽  
Genome Maintenance ◽  
Self Renewal ◽  
Genomic Aberrations

Pluripotent stem cells (PSCs) must maintain their proper genomic content in order to preserve appropriate self-renewal and differentiation capacities. However, their prolonged in vitro propagation, as well as the environmental culture conditions, present serious challenges to genome maintenance. Recent work has been focused on potential means to alleviate the genomic insults experienced by PSCs, and to detect them as soon as they arise, in order to prevent the detrimental consequences of these genomic aberrations on PSC application in basic research and regenerative medicine.

Salivary Gland Hypofunction and Xerostomia in Head and Neck Radiation Patients

2019 ◽  
Vol 2019 (53) ◽  
Author(s):  
Siri Beier Jensen ◽  
Arjan Vissink ◽  
Kirsten H Limesand ◽  
Mary E Reyland
Keyword(s):  
Radiation Therapy ◽  
Head And Neck Cancer ◽  
Salivary Gland ◽  
Head And Neck ◽  
Neck Cancer ◽  
Radiation Injury ◽  
Salivary Gland Tissue ◽  
Gland Tissue ◽  
Salivary Gland Hypofunction ◽  
Gland Function

AbstractBackgroundThe most manifest long-term consequences of radiation therapy in the head and neck cancer patient are salivary gland hypofunction and a sensation of oral dryness (xerostomia).MethodsThis critical review addresses the consequences of radiation injury to salivary gland tissue, the clinical management of salivary gland hypofunction and xerostomia, and current and potential strategies to prevent or reduce radiation injury to salivary gland tissue or restore the function of radiation-injured salivary gland tissue.ResultsSalivary gland hypofunction and xerostomia have severe implications for oral functioning, maintenance of oral and general health, and quality of life. Significant progress has been made to spare salivary gland function chiefly due to advances in radiation techniques. Other strategies have also been developed, e.g., radioprotectors, identification and preservation/expansion of salivary stem cells by stimulation with cholinergic muscarinic agonists, and application of new lubricating or stimulatory agents, surgical transfer of submandibular glands, and acupuncture.ConclusionMany advances to manage salivary gland hypofunction and xerostomia induced by radiation therapy still only offer partial protection since they are often of short duration, lack the protective effects of saliva, or potentially have significant adverse effects. Intensity-modulated radiation therapy (IMRT), and its next step, proton therapy, have the greatest potential as a management strategy for permanently preserving salivary gland function in head and neck cancer patients.Presently, gene transfer to supplement fluid formation and stem cell transfer to increase the regenerative potential in radiation-damaged salivary glands are promising approaches for regaining function and/or regeneration of radiation-damaged salivary gland tissue.

scholarly journals In vitro neoplastic transformation of newborn hamster salivary-gland tissue by oncogenic DNA viruses

Cancer ◽  
1966 ◽  
Vol 19 (10) ◽  
pp. 1411-1415 ◽  
Author(s):  
Samuel A. Wells ◽  
Alan S. Rabson ◽  
Richard A. Malmgren ◽  
Alfred S. Ketcham
Keyword(s):  
Salivary Gland ◽  
Neoplastic Transformation ◽  
Dna Viruses ◽  
Salivary Gland Tissue ◽  
Gland Tissue ◽  
Newborn Hamster

scholarly journals Generation of mature compact ventricular cardiomyocytes from human pluripotent stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shunsuke Funakoshi ◽  
Ian Fernandes ◽  
Olya Mastikhina ◽  
Dan Wilkinson ◽  
Thinh Tran ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Target Population ◽  
Cell Types ◽  
Human Pluripotent Stem Cells ◽  
Differentiation Strategy ◽  
Ventricular Cardiomyocytes ◽  
Ventricular Cells ◽  
Key Aspects

AbstractCompact cardiomyocytes that make up the ventricular wall of the adult heart represent an important therapeutic target population for modeling and treating cardiovascular diseases. Here, we established a differentiation strategy that promotes the specification, proliferation and maturation of compact ventricular cardiomyocytes from human pluripotent stem cells (hPSCs). The cardiomyocytes generated under these conditions display the ability to use fatty acids as an energy source, a high mitochondrial mass, well-defined sarcomere structures and enhanced contraction force. These ventricular cells undergo metabolic changes indicative of those associated with heart failure when challenged in vitro with pathological stimuli and were found to generate grafts consisting of more mature cells than those derived from immature cardiomyocytes following transplantation into infarcted rat hearts. hPSC-derived atrial cardiomyocytes also responded to the maturation cues identified in this study, indicating that the approach is broadly applicable to different subtypes of the heart. Collectively, these findings highlight the power of recapitulating key aspects of embryonic and postnatal development for generating therapeutically relevant cell types from hPSCs.

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