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Behnaz Banimohammad Shotorbani, Helder André, Abolfazl Barzegar, Nosratollah Zarghami, Roya Salehi, Effat Alizadeh
Cell sheet technology aims at replacement of artificial extracellular matrix (ECM) or scaffolds, popular in tissue engineering, with natural cell derived ECM. Adipose tissue mesenchymal stem cells (ASCs) have the ability of ECM secretion and presented promising outcomes in clinical trials. As well, different studies found that secretome of ASCs could be suitable for triggering cell free regeneration induction. The aim of this study was to investigate the effect of using two bio-factors: secretome of ASCs (SE) and vitamin C (VC) for cell sheet engineering on a thermosensitive poly N-isopropyl acryl amide-Methacrylic acid (P(NIPAAm-MAA)) hydrogel...
November 3, 2018: Journal of Materials Science. Materials in Medicine
Zhao Wei, Haiyang Guo, Junchao Qin, Shihua Lu, Qiao Liu, Xiyu Zhang, Yongxin Zou, Yaoqin Gong, Changshun Shao
Cellular senescence, an irreversible proliferative arrest, functions in tissue remodeling during development and is implicated in multiple aging-associated diseases. While senescent cells often manifest an array of senescence-associated phenotypes, such as cell cycle arrest, altered heterochromatin architecture, reprogrammed metabolism and senescence-associated secretory phenotype (SASP), the identification of senescence cells has been hindered by lack of specific and universal biomarkers. To systematically identify universal biomarkers of cellular senescence, we integrated multiple transcriptome data sets of senescent cells obtained through different in vitro manipulation modes as well as age-related gene expression data of human tissues...
November 1, 2018: Free Radical Biology & Medicine
Yong-Ho Lee, So Ra Kim, Dai Hoon Han, Hee Tae Yu, Yoon Dae Han, Jin Hee Kim, Soo Hyun Kim, Chan Joo Lee, Byoung-Hoon Min, Dong-Hyun Kim, Kyung Hwan Kim, Jin Won Cho, Won-Woo Lee, Eui-Cheol Shin, Sungha Park
Senescent T cells have been implicated in chronic inflammatory and cardiovascular diseases. Here, we explored the relationship between senescent T cells and glycemic status in a cohort of 805 participants by investigating the frequency of CD57+ or CD28null senescent T cells in peripheral blood. Normal glucose tolerance (NGT) participants with follow-up data (N = 149) were included to determine whether hyperglycemia (prediabetes or type 2 diabetes) developed during follow-up (mean 2.3 years). CD8+ CD57+ and CD8+ CD28null T cell frequencies were significantly higher in prediabetes and type 2 diabetes compared with NGT...
November 2, 2018: Diabetes
Chiara Fiorillo, Maria Rosaria D'Apice, Federica Trucco, Michela Murdocca, Paola Spitalieri, Stefania Assereto, Serena Baratto, Guido Morcaldi, Carlo Minetti, Federica Sangiuolo, Giuseppe Novelli
Mandibular hypoplasia, deafness, and progeroid features, with concomitant lipodystrophy, define a multisystem disorder named MDPL syndrome. MDPL has been associated with heterozygous mutations in POLD1 gene resulting in loss of DNA polymerase δ activity. In this study, we report clinical, genetic, and cellular studies of a 13-year-old Pakistani girl, presenting growth retardation, sensorineural deafness, altered distribution of subcutaneous adipose tissue, and insulin resistance. We performed Sanger sequencing of POLD1 gene in the proband and the healthy parents...
November 2, 2018: DNA and Cell Biology
Katarzyna Kornicka, Jolanta Szłapka-Kosarzewska, Agnieszka Śmieszek, Krzysztof Marycz
Obesity and endocrine disorders have become prevalent issues in the field of both human and veterinary medicine. Equine metabolic syndrome is a complex disorder involving alternation in metabolism and chronic systemic inflammation. It has been shown that unfavourable microenvironment of inflamed adipose tissue negatively affects adipose stem cell population (ASC) residing within, markedly limiting their therapeutic potential. ASCsEMS are characterized by increased senescence apoptosis, excessive accumulation of reactive oxygen species (ROS), mitochondria deterioration and "autophagic flux...
October 28, 2018: Journal of Cellular and Molecular Medicine
Jia Fang, Yuan Yan, Xin Teng, Xinyu Wen, Na Li, Sha Peng, Wenshuai Liu, F Xavier Donadeu, Shanting Zhao, Jinlian Hua
Transplantation of adipose-derived mesenchymal stem cells (ADMSCs) can aid in the treatment of numerous diseases in animals. However, natural aging during in vitro expansion of ADMSCs prior to their use in transplantation restricts their beneficial effects. Melatonin is reported to exert biorhythm regulation, anti-oxidation, and anti-senescence effects in various animal and cell models. Herein, by using a senescent canine ADMSCs (cADMSCs) cell model subjected to multiple passages in vitro , we investigated the effects of melatonin on ADMSCs senescence...
October 25, 2018: Aging
Radhakrishnan Vishnubalaji, Muthurangan Manikandan, Abdullah Aldahmash, Abdullah AlJarbou, Mohamad Habous, Dulaim Alhajeri, Raed Almannie, Musaad Alfayez, Nehad M Alajez, Saleh Binsaleh
BACKGROUND: Stem cell-based therapies have recently been explored in the field of erectile dysfunction (ED). However, the cellular and molecular phenotype of adipose derived stem cells (ADSCs) stromal vascular fraction (SVF) from ED patients remains largely unknown. Herein we compared the global gene expression profile in the SVF from ED patients and healthy individuals and identified altered signaling pathways between the two groups. METHODS: Samples (2-5g) of abdominal adipose tissue from ED patients (n=6) and healthy individual controls (n=3) undergoing elective cosmetic liposuction were collected...
October 17, 2018: Bioscience Reports
Abbas Ishaq, Damien Dufour, Kerry Cameron, Thomas von Zglinicki, Gabriele Saretzki
Dietary restriction (DR) is thought to exert its beneficial effects on healthspan at least partially by a senolytic and senostatic action, i.e. by reducing frequencies of cells with markers of DNA damage and senescence in multiple tissues. Due to its importance in metabolic and inflammation regulation, fat is a prime tissue for health span determination as well as a prime target for DR. We aimed to determine here whether the beneficial effects of DR would be retained over a subsequent period of ad libitum (AL) feeding...
October 10, 2018: Experimental Gerontology
Raheleh Farahzadi, Ezzatollah Fathi, Seyed Alireza Mesbah-Namin, Nosratollah Zarghami
The identification of factors that reduce the senescent tendency of the mesenchymal stem cells (MSCs) upon expansion has great potential for cellular therapies in regenerative medicine. Previous studies have shown the aging protective effect of L-carnitine (LC). On the other hand, reduction in proliferation potential and age-dependent decline in number and functions of MSCs were accompanied by telomere shortening, reduction in telomerase activity and epigenetic changes. The aim of this study was to evaluate the effects of LC on aging of MSCs through telomerase activity assessment and the investigation of methylation status of the hTERT gene promoter...
October 2018: Tissue & Cell
Durgesh Kumar, Sanket Kumar Pandya, Salil Varshney, Kripa Shankar, Sujith Rajan, Ankita Srivastava, Abhishek Gupta, Sanchita Gupta, Achchhe Lal Vishwakarma, Amit Misra, Anil N Gaikwad
BACKGROUND/OBJECTIVES: Chronic low-grade inflammation/meta-inflammation in adipose tissue leads to obesity-associated metabolic complications. Despite growing understanding, the roles of immune cell subsets, their interrelationship, and chronological events leading to progression of obesity-associated insulin resistance (IR) remains unclear. METHODS: We carried out temporal immunometabolic profiling of adipose tissue from C57BL/6 mice fed a high-fat diet (HFD) for 4, 8, 12, 16, and 20 weeks...
October 9, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Matthew J Yousefzadeh, Yi Zhu, Sara J McGowan, Luise Angelini, Heike Fuhrmann-Stroissnigg, Ming Xu, Yuan Yuan Ling, Kendra I Melos, Tamar Pirtskhalava, Christina L Inman, Collin McGuckian, Erin A Wade, Jonathon I Kato, Diego Grassi, Mark Wentworth, Christin E Burd, Edgar A Arriaga, Warren L Ladiges, Tamara Tchkonia, James L Kirkland, Paul D Robbins, Laura J Niedernhofer
BACKGROUND: Senescence is a tumor suppressor mechanism activated in stressed cells to prevent replication of damaged DNA. Senescent cells have been demonstrated to play a causal role in driving aging and age-related diseases using genetic and pharmacologic approaches. We previously demonstrated that the combination of dasatinib and the flavonoid quercetin is a potent senolytic improving numerous age-related conditions including frailty, osteoporosis and cardiovascular disease. The goal of this study was to identify flavonoids with more potent senolytic activity...
October 2018: EBioMedicine
Nhat Chau Truong, Khanh Hong-Thien Bui, Phuc Van Pham
INTRODUCTION: Since the 1980s, adipose-derived stem cells (ASCs) have become a powerful and potential source for stem cell-based therapy, regenerative medicine, and even drug delivery in cancer treatment. The development of off-the-shelf mesenchymal stem cells (MSCs), including ASCs, has rapidly advanced in recent years with several clinical trials and approved products. In this technology, ASCs should be expanded long term in order to harvest higher cell number. In this study, senescence of ASCs after long-term expansion was evaluated...
September 22, 2018: Advances in Experimental Medicine and Biology
Y Meng, A Eirin, X-Y Zhu, H Tang, L J Hickson, A Lerman, A J van Wijnen, L O Lerman
Mesenchymal stem cells (MSCs) constitute an important repair system, but may be impaired by exposure to cardiovascular risk factors. Consequently, adipose tissue-derived MSCs from pigs with the metabolic syndrome (MetS) show decreased vitality. A growing number of microRNAs (miRNAs) are recognized as key modulators of senescence, but their role in regulating senescence in MSC in MetS is unclear. We tested the hypothesis that MetS upregulates in MSC expression of miRNAs that can serve as post-transcriptional regulators of senescence-associated (SA) genes...
October 2018: Cell Transplantation
Roberta Fajka-Boja, Annamária Marton, Anna Tóth, Péter Blazsó, Vilmos Tubak, Balázs Bálint, István Nagy, Zoltán Hegedűs, Csaba Vizler, Robert L Katona
BACKGROUND: Adipose-tissue stem cells (ASCs) are subject of intensive research since their successful use in regenerative therapy. The drawback of ASCs is that they may serve as stroma for cancer cells and assist tumor progression. It is disquieting that ASCs frequently undergo genetic and epigenetic changes during their in vitro propagation. In this study, we describe the polyploidization of murine ASCs and the accompanying phenotypical, gene expressional and functional changes under long term culturing...
September 5, 2018: BMC Cancer
Jelena Krstic, Isabel Reinisch, Michael Schupp, Tim J Schulz, Andreas Prokesch
As a tumor suppressor and the most frequently mutated gene in cancer, p53 is among the best-described molecules in medical research. As cancer is in most cases an age-related disease, it seems paradoxical that p53 is so strongly conserved from early multicellular organisms to humans. A function not directly related to tumor suppression, such as the regulation of metabolism in nontransformed cells, could explain this selective pressure. While this role of p53 in cellular metabolism is gradually emerging, it is imperative to dissect the tissue- and cell-specific actions of p53 and its downstream signaling pathways...
September 4, 2018: International Journal of Molecular Sciences
Antonia Graja, Sabrina Gohlke, Tim J Schulz
Brown adipose tissue aging and the concomitant loss of thermogenic capacity have been linked to an inability to maintain normal energy homeostasis in late life. Similarly, the ability of white fat to convert into brite/beige adipose tissue declines. This may ultimately exacerbate the progression of age-related metabolic pathologies, such as insulin resistance and obesity. The depletion of all types of brown adipocytes during aging is well-established and has been described in rodent models as well as humans...
August 24, 2018: Handbook of Experimental Pharmacology
Zhuohao Liu, Leigang Jin, Jin-Kui Yang, Baile Wang, Kelvin K L Wu, Philip Hallenborg, Aimin Xu, Kenneth K Y Cheng
Profound loss and senescence of adipose tissues are hallmarks of advanced age, but the underlying cause and their metabolic consequences remain obscure. Proper function of the murine double minute 2 (MDM2)-p53 axis is known to prevent tumorigenesis and several metabolic diseases, yet its role in regulation of adipose tissue aging is still poorly understood. In this study, we show that the proximal p53 inhibitor MDM2 is markedly downregulated in subcutaneous white and brown adipose tissues of mice during aging...
November 2018: Diabetes
Zhengjie Wang, Xiaolong Xu, Yi Liu, Yongheng Gao, Fei Kang, Baohua Liu, Jing Wang
Brown adipose tissue (BAT) is an important energy metabolic organ that is highly implicated in obesity, type 2 diabetes, and atherosclerosis. Aging is one of the most important determinants of BAT activity. In this study, we used 18 F-FDG PET/CT imaging to assess BAT aging in Lmna-/- mice. The maximum standardized uptake value (SUVMax ) of the BAT was measured, and the target/nontarget (T/NT) values of BAT were calculated. The transcription and the protein expression levels of the uncoupling protein 1 (UCP1), beta3-adrenergic receptor ( β 3-AR), and the PR domain-containing 16 (PRDM16) were measured by quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting or immunohistochemical analysis...
2018: Contrast Media & Molecular Imaging
Tomoya Yamada, Mituru Kamiya, Mikito Higuchi, Naoto Nakanishi
Obesity is associated with the chronic inflammation and senescence of adipose tissues. Macrophage is a key mediator of chronic inflammation that infiltrates obese adipose tissue and stimulates metabolic disorders. However, the fat depot-specific differences of macrophage infiltration and senescence, especially the influence on intramuscular adipose tissue, have remained unclear. We investigated the fat depot-specific differences of macrophage infiltration and senescence in obese bovine adipose tissue from three different anatomical sites (subcutaneous, intramuscular and visceral)...
October 10, 2018: Journal of Veterinary Medical Science
Barbara Bellei, Emilia Migliano, Marinella Tedesco, Silvia Caputo, Federica Papaccio, Gianluca Lopez, Mauro Picardo
BACKGROUND: Adipose tissue-derived stem cells are considered to be a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using adipose tissue or purified stem cells, intercellular molecule exchange by the adipose tissue complex, a vast array of bioactive secretory factors, demonstrated beneficial effects by reducing tissue damage and stimulation of endogenous repair. However, for therapeutic purposes, the use of secretome derivatives, such as full conditioned media or purified exosomes generated in vitro, may present considerable disadvantages for cell manufacturing, storage, product safety, and their potential as a ready-to-go therapeutic product...
August 9, 2018: Stem Cell Research & Therapy
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