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Beta cells AND Redifferentiation

Yi-Tian Li, Xiao-Ting Tian, Mo-Li Wu, Xu Zheng, Qing-You Kong, Xiao-Xin Cheng, Guang-Wen Zhu, Jia Liu, Hong Li
Anaplastic thyroid cancer (ATC) is a highly lethal undifferentiated malignancy without reliable therapies. Retinoic acid (RA) has been employed to promote redifferentiation of thyroid cancers by increasing their I131 uptake and radio-sensitivity, but its effect(s) on ATCs has not yet been ascertained. Likewise, resveratrol induces cancer redifferentiation but, also in this case, its effects on ATCs remain unknown. These issues have been addresses in the current study using three human ATC cell lines (THJ-11T, THJ-16T, and THJ-21T) through multiple experimental approaches...
March 29, 2018: International Journal of Molecular Sciences
Caterina Aloy-Reverté, José L Moreno-Amador, Montserrat Nacher, Eduard Montanya, Carlos E Semino
Islet transplantation has provided proof of concept that cell therapy can restore normoglycemia in patients with diabetes. However, limited availability of islet tissue severely restricts the clinical use of the treatment. Thus, there is an urgent need to develop new strategies to generate an abundant source of insulin-producing cells that could be used to treat diabetes. A potential approach is the in vitro expansion of pancreatic beta cells obtained from cadaveric organ donors. However, when human beta cells are expanded in vitro, they dedifferentiate and lose the expression of insulin, probably as a consequence of pancreatic islet dissociation into single cells...
March 2018: Tissue Engineering. Part A
Frank Martin, Mario Lehmann, Ulrich Sack, Ursula Anderer
Personalized features in the treatment of knee injuries and articular replacement therapies play an important role in modern life with increasing demand. Therefore, cell-based therapeutic approaches for the regeneration of traumatic defects of cartilage tissue were developed. However, great variations in the quality of repair tissue or therapeutic outcome were observed. The aim of the study was to capture and visualize individual differentiation capacities of chondrocytes derived from different donors with regard to a possible personal regeneration capacity using a cell-based therapy...
December 2017: Experimental Biology and Medicine
Andrew R Mendelsohn, James W Larrick, Jennifer L Lei
Epigenetic variation with age is one of the most important hallmarks of aging. Resetting or repairing the epigenome of aging cells in intact animals may rejuvenate the cells and perhaps the entire organism. In fact, differentiated adult cells, which by definition have undergone some epigenetic changes, are capable of being rejuvenated and reprogrammed to create pluripotent stem cells and viable cloned animals. Apparently, such reprogramming is capable of completely resetting the epigenome. However, attempts to fully reprogram differentiated cells in adult animals have failed in part because reprogramming leads to the formation of teratomas...
April 2017: Rejuvenation Research
Vanessa J Bianchi, Joanna F Weber, Stephen D Waldman, David Backstein, Rita A Kandel
OBJECTIVE: When serially passaged in standard monolayer culture to expand cell number, articular chondrocytes lose their phenotype. This results in the formation of fibrocartilage when they are used clinically, thus limiting their use for cartilage repair therapies. Identifying a way to redifferentiate these cells in vitro is critical if they are to be used successfully. Transforming growth factor beta (TGFβ) family members are known to be crucial for regulating differentiation of fetal limb mesenchymal cells and mesenchymal stromal cells to chondrocytes...
February 2017: Tissue Engineering. Part A
Mitsugu Omata, Yukiko Doke, Chikaomi Yamada, Kayoko Kawashima, Rumiko Sho, Kei Enomoto, Mayumi Furuya, Norio Inomata
Tubular epithelial cells (TECs) can be dedifferentiated by repetitive insults, which activate scar-producing cells generated from interstitial cells such as fibroblasts, leading to the accumulation and deposition of extracellular matrix molecules. The dedifferentiated TECs play a crucial role in the development of renal fibrosis. Therefore, renal fibrosis may be attenuated if dedifferentiated TECs are converted back to their normal state (re-epithelialization). However, the mechanism underlying the re-epithelialization remains to be elucidated...
2016: PloS One
Dongli Yue, Zhen Zhang, Jieyao Li, Xinfeng Chen, Yu Ping, Shasha Liu, Xiaojuan Shi, Lifeng Li, Liping Wang, Lan Huang, Bin Zhang, Yan Sun, Yi Zhang
Esophageal cancer is one of the most lethal solid malignancies. Mounting evidence demonstrates that cancer stem cells (CSCs) are able to cause tumor initiation, metastasis and responsible for chemotherapy and radiotherapy failures. As CSCs are thought to be the main reason of therapeutic failure, these cells must be effectively targeted to elicit long-lasting therapeutic responses. We aimed to enrich and identify the esophageal cancer cell subpopulation with stem-like properties and help to develop new target therapy strategies for CSCs...
August 1, 2015: Experimental Cell Research
Gabriele D'Uva, Alla Aharonov, Mattia Lauriola, David Kain, Yfat Yahalom-Ronen, Silvia Carvalho, Karen Weisinger, Elad Bassat, Dana Rajchman, Oren Yifa, Marina Lysenko, Tal Konfino, Julius Hegesh, Ori Brenner, Michal Neeman, Yosef Yarden, Jonathan Leor, Rachel Sarig, Richard P Harvey, Eldad Tzahor
The murine neonatal heart can regenerate after injury through cardiomyocyte (CM) proliferation, although this capacity markedly diminishes after the first week of life. Neuregulin-1 (NRG1) administration has been proposed as a strategy to promote cardiac regeneration. Here, using loss- and gain-of-function genetic tools, we explore the role of the NRG1 co-receptor ERBB2 in cardiac regeneration. NRG1-induced CM proliferation diminished one week after birth owing to a reduction in ERBB2 expression. CM-specific Erbb2 knockout revealed that ERBB2 is required for CM proliferation at embryonic/neonatal stages...
May 2015: Nature Cell Biology
Ivan A Valdez, Adrian K K Teo, Rohit N Kulkarni
Controversy has long surrounded research on pancreatic beta cell regeneration. Some groups have used nonphysiological experimental methodologies to build support for the existence of pancreatic progenitor cells within the adult pancreas that constantly replenish the beta cell pool; others argue strongly against this mode of regeneration. Recent research has reinvigorated enthusiasm for the harnessing of pancreatic plasticity for therapeutic application--for example, the transdifferentiation of human pancreatic exocrine cells into insulin-secreting beta-like cells in vitro; the conversion of mouse pancreatic acinar cells to beta-like cells in vivo via cytokine treatment; and the potential redifferentiation of dedifferentiated mouse beta cells in vivo...
February 4, 2015: Science Translational Medicine
Hoshang J Unwalla, Pedro Ivonnet, John S Dennis, Gregory E Conner, Matthias Salathe
Chronic bronchitis, caused by cigarette smoke exposure, is characterized by mucus hypersecretion and reduced mucociliary clearance (MCC). Effective MCC depends, in part, on adequate airway surface liquid. Cystic fibrosis transmembrane conductance regulator (CFTR) provides the necessary osmotic gradient for serosal to mucosal fluid transport through its ability to both secrete Cl(-) and regulate paracellular permeability, but CFTR activity is attenuated in chronic bronchitis and in smokers. β2-adrenergic receptor (β2-AR) agonists are widely used for managing chronic obstructive pulmonary disease, and can activate CFTR, stimulate ciliary beat frequency, and increase epithelial permeability, thereby stimulating MCC...
January 2015: American Journal of Respiratory Cell and Molecular Biology
Jose Diaz-Romero, Aurelie Quintin, Eric Schoenholzer, Chantal Pauli, Alain Despont, Matthias A Zumstein, Sandro Kohl, Dobrila Nesic
Many studies in the field of cell-based cartilage repair have focused on identifying markers associated with the differentiation status of human articular chondrocytes (HAC) that could predict their chondrogenic potency. A previous study from our group showed a correlation between the expression of S100 protein in HAC and their chondrogenic potential. The aims of the current study were to clarify which S100 proteins are associated with HAC differentiation status and to provide an S100-based assay for measuring HAC chondrogenic potential...
August 2014: Journal of Cellular Physiology
Eunmee Hong, A Hari Reddi
Articular cartilage contains three functional zones (superficial, middle, and deep) characterized by distinct structure, composition, and biomechanical properties. One of the unsolved major challenges in cartilage tissue engineering is to produce tissue that mimics the zonal organization of the native articular cartilage. An increasing number of studies aim to design zonal organization into tissue-engineered cartilage by forming a stratified construct using zonal cell subpopulations. However, in vitro monolayer expansion of chondrocytes, which is generally required to obtain high cell numbers necessary for tissue engineering and autologous chondrocyte implantation, leads to dedifferentiation of chondrocytes into fibroblast-like cells, resulting in loss of zonal markers, such as the superficial zone protein (SZP) of the superficial zone as well as chondrocytic phenotype markers, such as type II collagen and aggrecan...
April 2013: Tissue Engineering. Part A
Alexander Kaplun, Sijana Dzinic, M Bernardo, Shijie Sheng
Maspin, a class II tumor suppressor, is often downregulated during tumor progression and its depletion from the nucleus is associated with poor prognosis. Recently, we reported that reintroduction of maspin is sufficient for redifferentiation of prostate cancer cells to epithelial phenotype, a reversal of epithelial-to-mesenchymal transition. We have linked this effect of maspin with its ability to directly inhibit HDAC1, thereby influencing the acetylation state of transcription factors and other proteins...
2012: Critical Reviews in Eukaryotic Gene Expression
Meera Raymond, Tania Marchbank, Mary P Moyer, Raymond J Playford, Ian R Sanderson, Laurens Kruidenier
Subepithelial myofibroblasts are involved in the initiation and coordination of intestinal epithelial repair, but the molecular signaling pathways are largely unknown. The cellular adaptations that occur during repair range from dedifferentiation and migration to proliferation and redifferentiation, in a way that is strongly reminiscent of normal crypt-to-villus epithelial maturation. We therefore hypothesized that Wnt/β-catenin signaling may have a pivotal role in intestinal epithelial wound repair. We used the established scratch wound method in Caco-2 cells and in nontransformed NCM460 cells to monitor the effects of IL-1β-stimulated colonic myofibroblasts (CCD-18co) on intestinal epithelial repair, with immunoblotting and immunodepletion to examine the conditioned media...
December 1, 2012: American Journal of Physiology. Gastrointestinal and Liver Physiology
Hoshang J Unwalla, Gabor Horvath, Felix D Roth, Gregory E Conner, Matthias Salathe
Although inhaled bronchodilators are commonly used in the treatment of airway disease to dilate airway smooth muscle, little is known regarding the mechanisms that regulate albuterol movement across the epithelium to reach its target, the airway smooth muscle. Because the rate of onset depends on the transepithelial transport of albuterol, to determine the mechanisms that regulate the transepithelial movement of albuterol is essential. Human bronchial epithelial cells, fully redifferentiated in culture at the air-liquid interface, were used to study the cellular uptake and total transepithelial flux of (3)H-albuterol from the apical to the basolateral surfaces...
April 2012: American Journal of Respiratory Cell and Molecular Biology
Holger A Russ, Elad Sintov, Leeat Anker-Kitai, Orr Friedman, Ayelet Lenz, Ginat Toren, Chen Farhy, Metsada Pasmanik-Chor, Varda Oron-Karni, Philippe Ravassard, Shimon Efrat
BACKGROUND: Expansion of beta cells from the limited number of adult human islet donors is an attractive prospect for increasing cell availability for cell therapy of diabetes. However, attempts at expanding human islet cells in tissue culture result in loss of beta-cell phenotype. Using a lineage-tracing approach we provided evidence for massive proliferation of beta-cell-derived (BCD) cells within these cultures. Expansion involves dedifferentiation resembling epithelial-mesenchymal transition (EMT)...
2011: PloS One
Juan A Montero, Carlos I Lorda-Diez, Juan M Hurlé
Progress in medicine over recent decades has notably increased life expectancy in the Western world. Such advance implies that the treatment of degenerative processes associated with ageing has become one of the major tasks of current medicine and therapeutics. High expectation relies on stem cell research in order to apply cell therapies to ameliorate degenerative processes, remarkably those concerning the circulatory, locomotor and nervous systems. However, the skeletal connective tissues have revealed that cell plasticity is a factor of major importance in regenerative therapies...
May 2012: Journal of Tissue Engineering and Regenerative Medicine
Kim Biermann, Hans-Jürgen Biersack, Amir Sabet, Viktor Janzen
The prognosis of patients with surgically unresectable differentiated thyroid tumors deteriorates significantly if radioiodine therapy is or becomes ineffective, considering the limited role of conventional chemotherapies in these patients. Several alternative approaches have been investigated for the treatment of patients with advanced thyroid malignancies in recent years. Among targeted therapies, tyrosine kinase inhibitors have resulted in the most encouraging responses and could soon be, along with redifferentiation therapy, the possible palliative strategies...
March 2011: Seminars in Nuclear Medicine
Wan-Chun Li, J Michael Rukstalis, Wataru Nishimura, Vaja Tchipashvili, Joel F Habener, Arun Sharma, Susan Bonner-Weir
The adult pancreas has considerable capacity to regenerate in response to injury. We hypothesized that after partial pancreatectomy (Px) in adult rats, pancreatic-duct cells serve as a source of regeneration by undergoing a reproducible dedifferentiation and redifferentiation. We support this hypothesis by the detection of an early loss of the ductal differentiation marker Hnf6 in the mature ducts, followed by the transient appearance of areas composed of proliferating ductules, called foci of regeneration, which subsequently form new pancreatic lobes...
August 15, 2010: Journal of Cell Science
Masashi Nakagawa, Takahiko Naruko, Yoshihiro Ikura, Ryushi Komatsu, Yoko Iwasa, Chizuko Kitabayashi, Takeshi Inoue, Akira Itoh, Minoru Yoshiyama, Makiko Ueda
AIM: This immunohistochemical investigation was to analyze the relationship between platelet activation/aggregation, inflammatory cell infiltration, the differentiation state of neointimal smooth muscle cells (SMCs), expression of platelet-derived growth factor (PDGF), and endothelial cell regeneration at sites of bare-metal stents (BMS) in patients with acute coronary syndrome (ACS). METHODS: Sixteen coronary arteries after stenting were obtained at autopsy from ACS patients...
July 30, 2010: Journal of Atherosclerosis and Thrombosis
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