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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
Wenyan Fu, Yang Liu, Christina Sun, Hang Yin
Aging of white adipose tissue (WAT) is associated with reduced insulin sensitivity, which contributes to whole-body glucose intolerance. WAT aging in mice impairs cold-induced beige adipocyte recruitment (beiging), which has been attributed to the senescence of adipose progenitor cells. Tumor suppressor p53 has also been implicated in WAT aging. However, whether p53-related cellular aging in mature white adipocytes is causative of age-impaired WAT beiging remains unknown. It is also unclear whether transient p53 inhibition can rescue WAT beiging...
July 27, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ming Xu, Tamar Pirtskhalava, Joshua N Farr, Bettina M Weigand, Allyson K Palmer, Megan M Weivoda, Christina L Inman, Mikolaj B Ogrodnik, Christine M Hachfeld, Daniel G Fraser, Jennifer L Onken, Kurt O Johnson, Grace C Verzosa, Larissa G P Langhi, Moritz Weigl, Nino Giorgadze, Nathan K LeBrasseur, Jordan D Miller, Diana Jurk, Ravinder J Singh, David B Allison, Keisuke Ejima, Gene B Hubbard, Yuji Ikeno, Hajrunisa Cubro, Vesna D Garovic, Xiaonan Hou, S John Weroha, Paul D Robbins, Laura J Niedernhofer, Sundeep Khosla, Tamara Tchkonia, James L Kirkland
Physical function declines in old age, portending disability, increased health expenditures, and mortality. Cellular senescence, leading to tissue dysfunction, may contribute to these consequences of aging, but whether senescence can directly drive age-related pathology and be therapeutically targeted is still unclear. Here we demonstrate that transplanting relatively small numbers of senescent cells into young mice is sufficient to cause persistent physical dysfunction, as well as to spread cellular senescence to host tissues...
July 9, 2018: Nature Medicine
Maria I Guillén, Julia Platas, María D Pérez Del Caz, Vicente Mirabet, Maria J Alcaraz
The inflammatory process is an essential phenomenon in the induction of immune responses. Monocytes are key effector cells during the inflammatory process. A wide range of evidence indicates that mesenchymal stem cells from adipose tissue (ASC) are endowed with immunomodulatory capacity. However, the interaction between ASC and monocytes in the innate immune response is not well understood. The aim of this work was to investigate the possible paracrine anti-inflammatory effects of ASC in human monocytes. Monocytes were isolated from buffy coats and ASC from fat of non-obese patients...
2018: Frontiers in Physiology
Sergio Perez-Diaz, Maria P Garcia-Sobreviela, Yolanda Gonzalez-Irazabal, Beatriz Garcia-Rodriguez, Silvia Espina, Izaskun Arenaz, Jose M Arbones-Mainar
Adipose tissue (AT) expands under obesogenic conditions. Yet, when the growth exceeds a certain limit, AT becomes dysfunctional and surplus lipids start depositing ectopically. Polymerase I and transcription release factor (PTRF) has been proposed as a mechanism leading to a dysfunctional AT by decreasing the adipogenic potential of human adipocyte precursors. However, whether or not PTRF can be secreted by the adipocytes into the bloodstream is not yet known. For this work, PTRF presence was investigated in plasma...
June 4, 2018: Journal of Physiology and Biochemistry
Marianna Kunrath-Lima, Marcelo Coutinho de Miranda, Andrea da Fonseca Ferreira, Camila Cristina Fraga Faraco, Mariane Izabella Abreu de Melo, Alfredo Miranda Goes, Michele Angela Rodrigues, Jerusa Araújo Quintão Arantes Faria, Dawidson Assis Gomes
Ca2+ is an important second messenger, and it is involved in many cellular processes such as cell death and proliferation. The rise in intracellular Ca2+ levels can be due to the generation of inositol 1,4,5-trisphosphate (InsP3 ), which is a product of phosphatidylinositol 4,5-bisphosphate (PIP2 ) hydrolysis by phospholipases C (PLCs), that leads to Ca2+ release from endoplasmic reticulum by InsP3 receptors (InsP3 R). Ca2+ signaling patterns can vary in different regions of the cell and increases in nuclear Ca2+ levels have specific biological effects that differ from those of Ca2+ increase in the cytoplasm...
September 2018: Cellular Signalling
Sean Delaney, Russell W H Kridel
Background: The midface is particularly prone to the senescent changes of soft tissue ptosis and volume loss, which in individuals with aging or low adiposity can manifest as submalar hollowing. Facelift alone in those with submalar hollowing inadequately addresses the volume loss and may result in a gaunt appearance postoperatively. Submalar implant augmentation is a powerful tool for permanent midface volume restoration for a more youthful and natural contour, as opposed to soft tissue fillers that diminish over time...
May 28, 2018: Aesthetic Surgery Journal
Bauyrzhan Umbayev, Abdul-Razak Masoud, Andrey Tsoy, Dauren Alimbetov, Farkhad Olzhayev, Alla Shramko, Aiym Kaiyrlykyzy, Yuliya Safarova, Terence Davis, Sholpan Askarova
Mesenchymal stem cells (MSCs) represent a promising cell source for cellular therapy and tissue engineering and are currently being tested in a number of clinical trials for various diseases. However, like other somatic cells, MSCs age, and this senescence is accompanied by a progressive decline in stem cell function. Several lines of evidence suggest a role for the Rho family GTPase Cdc42 activity in cellular senescence processes. In the present study, we have examined aging-associated Cdc42 activity in rat adipose-derived mesenchymal stem cells (ADMSCs) and the consequences of pharmacological inhibition of Cdc42 in ADMSCs from aged rats...
July 2018: Biogerontology
Tao Liu, Xiaorong Ma, Tianxiang Ouyang, Huiping Chen, Jun Lin, Jun Liu, Yan Xiao, Jie Yu, Yingying Huang
Stem cell senescence and exhaustion are considered important drivers of organismal aging, and human adipose-derived stem cells (ADSCs) have emerged as a promising cell source for cell-based therapy. However, aging and low survival rate compromise the optimal outcome of cell-based therapy due to oxidative stress in the graft areas. Oxidative stress has long been considered to be harmful to cells, nevertheless, in this study, we found that lower concentration of hydrogen peroxide (H2 O2 ) decreased the number of SA-βgal-immunopositive cells, which was ameliorated by inhibition of SIRT1...
October 1, 2018: International Journal of Biological Macromolecules
Chang Chen, Qi Tang, Yan Zhang, Mei Yu, Wei Jing, Weidong Tian
BACKGROUND: Although typically cultured at an atmospheric oxygen concentration (20-21%), adipose-derived stem cells (ASCs) reside under considerable low oxygen tension (physioxia) in vivo. In the present study, we explored whether and how physioxia could be a more effective strategy for culturing ASCs for transplantation. METHODS: After isolation, human ASCs were cultured under physioxia (2% O2 ) and hyperoxia (20% O2 ) until assayed. WST-8, Transwell, tube formation, β-galactosidase staining, and annexin V-FITC/PI assays were used to evaluate cell proliferation, migration, angiogenesis, senescence, and apoptosis, respectively...
May 24, 2018: Stem Cell Research & Therapy
Zhuoming Liu, Rudell Screven, Lynne Boxer, Michael J Myers, Lax R Devireddy
In this article, we report on the development of a defined serum-free medium capable of supporting the culture expansion of mesenchymal stromal/stem cells (MSCs) from canine adipose tissue (canine Ad-MSCs). The potential benefits of serum-free media can only be utilized if cells cultured in serum-free media maintain the same functional characteristics as cells cultured in serum-containing media. Therefore, we analyze the characteristics of canine Ad-MSCs cultured in this serum-free medium or in serum-containing medium through evaluation of growth kinetics, clonogenic capacity, senescence, and differentiation capacity...
July 2018: Tissue Engineering. Part C, Methods
Panithi Sukho, Jan Willem Hesselink, Nicole Kops, Jolle Kirpensteijn, Femke Verseijden, Yvonne M Bastiaansen-Jenniskens
Tissue healing is a highly complex process involving a cascade of biochemical and cellular events. Excessive inflammation can impair the healing response. Previous in vitro studies have shown that mesenchymal stromal cells can modulate macrophage-induced inflammation and, therefore, are promising candidates for cell-based therapies aimed at promoting tissue repair. Recently, cell sheets were introduced as a new method of delivering stromal cells to the repair site. The goal of the current study was to compare the effect of different types of stromal cell sheets on the inflammatory state of macrophages in vitro...
July 1, 2018: Stem Cells and Development
Hiroyuki Moriyama, Mariko Moriyama, Toshiyuki Ozawa, Daisuke Tsuruta, Taro Iguchi, Satoshi Tamada, Tatsuya Nakatani, Koichi Nakagawa, Takao Hayakawa
Human adipose-derived mesenchymal stromal cells (hASCs) are attractive for regenerative medicine, but their limited in vitro life span limits their therapeutic applicability. Recent data demonstrate that hypoxia may benefit the ex vivo culture of stem cells. Such cells exhibit a high level of glycolytic metabolism under hypoxic conditions. However, the physiological role of glycolytic activation and its underlying regulatory mechanism are incompletely understood. We have shown that when activated under conditions of 5% O2 , Notch signaling dramatically increases the rate of glycolysis, improves proliferation efficiency, prevents senescence, and maintains the multipotency of hASCs...
July 1, 2018: Stem Cells and Development
Lucia Andrade, Camila E Rodrigues, Samirah A Gomes, Irene L Noronha
Acute kidney injury (AKI), characterized by a sharp drop in glomerular filtration, continues to be a significant health burden because it is associated with high initial mortality, morbidity, and substantial health-care costs. There is a strong connection between AKI and mechanisms of senescence activation. After ischemic or nephrotoxic insults, a wide range of pathophysiological events occur. Renal tubular cell injury is characterized by cell membrane damage, cytoskeleton disruption, and DNA degradation, leading to tubular cell death by necrosis and apoptosis...
May 2018: Cell Transplantation
Hidetoshi Sugihara, Naomi Teramoto, Keitaro Yamanouchi, Takashi Matsuwaki, Masugi Nishihara
Sarcopenia is the age-related loss of skeletal muscle mass and function. Skeletal muscle comprises diverse progenitor cells, including mesenchymal progenitor cells (MPCs), which normally support myogenic cell function but cause a decline in skeletal muscle function after differentiating into fibrous/adipose tissue. Cellular senescence is a form of persistent cell cycle arrest caused by cellular stress, including oxidative stress, and is accompanied by the acquisition of senescence-associated secretory phenotype (SASP)...
April 25, 2018: Aging
Vuong Cat Khanh, Amin Firman Zulkifli, Chiho Tokunaga, Toshiharu Yamashita, Yuji Hiramatsu, Osamu Ohneda
In the body, different types of adipose tissue perform different functions, with brown and beige adipose tissues playing unique roles in dissipating energy. Throughout life, adipocytes are regenerated from progenitors, and this process is impaired by aging. One of the progenitors of adipocytes are mesenchymal stem cells (MSCs), which have recently become a promising tool for stem cell therapy. However, whether or not aging impairs the brown/beige adipocyte differentiation of adipose tissue-derived MSCs (AT-MSCs) remains unclear...
June 7, 2018: Biochemical and Biophysical Research Communications
Bo-Yeon Lee, Qiang Li, Woo-Jin Song, Hyung-Kyu Chae, Kyeong Kweon, Jin-Ok Ahn, Hwa-Young Youn
Cytotherapy with mesenchymal stem cells (MSCs) has been studied in many species, and often requires in vitro cell expansion to obtain therapeutic doses of stem cells. Because the characteristics of MSCs, such as self-renewal and multi-lineage differentiation, can be altered by long-term culture, it is important to maintain stemness during cultivation. This study assessed the changes in the characteristics of feline adipose tissue-derived (fAT)-MSCs during in vitro passaging. Stem cells isolated from the adipose tissue of donor cats were cultured for seven sub-passages...
June 29, 2018: Journal of Veterinary Medical Science
Yehua Rui, Shengyi Yang, Li-Hua Chen, Li-Qiang Qin, Zhongxiao Wan
Adipose tissue is a key organ with substantial senescent cell accumulation under both obesity and aging conditions. Chia seed is an ancient seed and is the richest plant source of α-linolenic acid. We aimed to determine how cellular senescence markers will be altered in adipose tissue of senescence-accelerated mouse-prone 8 (SAMP8) mice fed with high-fat diets (HFDs); and how chia seed can affect the above markers. SAMP8 mice and their control senescence-accelerated mouse-resistant 1 (SAMR1) were divided into four groups, that is, SAMR1 low-fat diet group (R1LF), SAMP8LF group (P8LF), SAMP8 high-fat group (P8HF), and SAMP8HF group supplemented with 10% chia seed (P8HC)...
April 13, 2018: Journal of Medicinal Food
Xue Li, Xiaoyun Xie, Weishuai Lian, Rongfeng Shi, Shilong Han, Haijun Zhang, Ligong Lu, Maoquan Li
Diabetic foot ulcers (DFU) increase the risks of infection and amputation in patients with diabetes mellitus (DM). The impaired function and senescence of endothelial progenitor cells (EPCs) and high glucose-induced ROS likely exacerbate DFUs. We assessed EPCs in 60 patients with DM in a hospital or primary care setting. We also evaluated the therapeutic effects of exosomes secreted from adipose-derived stem cells (ADSCs) on stress-mediated senescence of EPCs induced by high glucose. Additionally, the effects of exosomes and Nrf2 overexpression in ADSCs were investigated in vitro and in vivo in a diabetic rat model...
April 13, 2018: Experimental & Molecular Medicine
Kagaku Azuma, Qian Zhou, Kin-Ya Kubo
Although the understanding of the complex pathogenesis for osteoporosis is appreciable, the underlying mechanism is not yet fully elucidated. There is a great need to further characterize the available animal models in osteoporosis research. The senescence-accelerated mouse prone 6 (SAMP6) mice have been developed as the spontaneous experimental model for senile osteoporosis. Here, we provide a comprehensive overview of current research regarding the bone morphological and molecular alterations and the possible mechanisms involved in these changes...
April 4, 2018: Medical Molecular Morphology
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