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mitochondria in stem cells

Sachin Kumar, Marie-Dominique Filippi
Transmission electron microscopy (TEM) provides details of the cellular organization and ultrastructure. However, TEM analysis of rare cell populations, especially cells in suspension such as hematopoietic stem cells (HSCs), remains limited due to the requirement of a high cell number during sample preparation. There are a few cytospin or monolayer approaches for TEM analysis from scarce samples, but these approaches fail to get significant quantitative data from the limited number of cells. Here, an alternative and novel approach for sample preparation in TEM studies is described for rare cell populations that enables quantitative analysis...
October 12, 2016: Journal of Visualized Experiments: JoVE
Mercedes Fernández-Moreno, Tamara Hermida-Gómez, M Esther Gallardo, Andrea Dalmao-Fernández, Ignacio Rego-Pérez, Rafael Garesse, Francisco J Blanco
INTRODUCTION: The generation of Rho-0 cells requires the use of an immortalization process, or tumor cell selection, followed by culture in the presence of ethidium bromide (EtBr), incurring the drawbacks its use entails. The purpose of this work was to generate Rho-0 cells using human mesenchymal stem cells (hMSCs) with reagents having the ability to remove mitochondrial DNA (mtDNA) more safely than by using EtBr. METHODOLOGY: Two immortalized hMSC lines (3a6 and KP) were used; 143B...
2016: PloS One
Mariana Pavel, David C Rubinsztein
Autophagy (literally "self-eating") is an evolutionarily conserved degradation process where cytoplasmic components are engulfed by vesicles called autophagosomes, which are then delivered to lysosomes, where their contents are degraded. Under stress conditions, such as starvation or oxidative stress, autophagy is upregulated in order to degrade macromolecules and restore the nutrient balance. The source of membranes that participate in the initial formation of phagophores is still incompletely understood and many intracellular structures have been shown to act as lipid donors, including the endoplasmic reticulum, Golgi, nucleus, mitochondria and the plasma membrane...
October 18, 2016: FEBS Journal
Le Zhang, Liang Xu, Fengchun Zhang, Erina Vlashi
Experimental evidence suggest that breast tumors originate from breast cancer stem cells (BCSCs), and that mitochondrial biogenesis is essential for the anchorage-independent clonal expansion and survival of CSCs, thus rendering mitochondria a significant target for novel treatment approaches. One of the recognized side effects of the FDA-approved drug, doxycycline is the inhibition of mitochondrial biogenesis. Here we investigate the mechanism by which doxycycline exerts its inhibitory effects on the properties of breast cancer cells and BCSCs, such as mammosphere forming efficiency, invasion, migration, apoptosis, the expression of stem cell markers and epithelial-to-mesenchymal transition (EMT) related markers of breast cancer cells...
October 18, 2016: Cell Cycle
Kyoko Ito, Raphaël Turcotte, Jinhua Cui, Samuel E Zimmerman, Sandra Pinho, Toshihide Mizoguchi, Fumio Arai, Judith M Runnels, Clemens Alt, Julie Teruya-Feldstein, Jessica C Mar, Rajat Singh, Toshio Suda, Charles P Lin, Paul S Frenette, Keisuke Ito
A single hematopoietic stem cell (HSC) is capable of reconstituting hematopoiesis and maintaining homeostasis by balancing self-renewal and cell differentiation. The mechanisms of HSC division balance, however, are not yet defined. Here we demonstrate, by characterizing at the single cell level a purified and minimally heterogeneous Tie2(+) HSC population, that these top hierarchical HSCs preferentially undergo symmetric divisions. The induction of mitophagy, a quality-control process in mitochondria, plays an essential role in self-renewing expansion of Tie2(+) HSCs...
October 13, 2016: Science
Jia Zhenwei
Mitochondria are important intracellular organelles which provide energy for cellular activities through oxidative phosphorylation. Recently, mitochondria have been shown to exhibit peculiar features in pluripotent stem cells (PSCs), namely, PSCs rely mainly on glycolysis for energy supply in pluripotent states while mitochondrial oxidative phosphorylation function is gradually enhanced during PSCs differentiation. In contrast, during somatic reprogramming, the metabolic transition from mitochondrial oxidative phosphorylation to glycolysis is necessary for successful reprogramming...
July 20, 2016: Yi Chuan, Hereditas
Aleksandra Cvoro, Aleksandar Bajic, Aijun Zhang, Marisa Simon, Igor Golic, Douglas H Sieglaff, Mirjana Maletic-Savatic, Aleksandra Korac, Paul Webb
Thyroid hormone (TH) receptors (TRs α and β) are homologous ligand-dependent transcription factors (TFs). While the TRs display distinct actions in development, metabolic regulation and other processes, comparisons of TRα and TRβ dependent gene regulation mostly reveal similar mechanisms of action and few TR subtype specific genes. Here, we show that TRα predominates in multipotent human adipose derived stem cells (hADSC) whereas TRβ is expressed at lower levels and is upregulated during hADSC differentiation...
2016: PloS One
Yi-Chun Lin, Horng-Jyh Harn, Po-Cheng Lin, Ming-Hsi Chuang, Chun-Hung Chen, Shinn-Zong Lin, Tzyy-Wen Chiou
Human adipose-derived stem cells (ADSCs) are a promising source of autologous stem cells for personalized cell-based therapies. Culture expansion of ADSCs provides an attractive opportunity for liver cirrhosis patients. However, safety and stability issues can pose big challenges for personalized autologous stem cell products. In the present study, we addressed whether the commercial production program could provide a consistent product for liver cirrhosis therapy. We collected adipose tissue from three human donors by lipoaspirate and isolated ADSCs, which were expanded in culture to reach 1 × 10(8) cells (an approximately 1000-fold expansion) within four passages...
October 6, 2016: Cell Transplantation
Qingshan Wang, Guohua Sun, Chenxue Gao, Lina Feng, Yan Zhang, Jie Hao, Enjun Zuo, Cong Zhang, Shuangyue Li, Fengyuan Piao
Growing evidence suggests that the increased neuronal apoptosis is involved in n-hexane-induced neuropathy. We have recently reported that bone marrow-mesenchymal stem cells-derived conditioned medium (BMSC-CM) attenuated 2,5-hexanedione (HD, the active metabolite of n-hexane)-induced apoptosis in PC12 cells. Here, we explored the anti-apoptotic efficacy of BMSC in vivo. HD-treated rats received BMSC by tail vein injection 5 weeks after HD intoxication. We found that in grafted rats, BMSC significantly attenuated HD-induced neuronal apoptosis in the spinal cord, which was associated with elevation of nerve growth factor (NGF)...
October 5, 2016: Scientific Reports
Seiya Arita, Yuta Kinoshita, Kaori Ushida, Atsushi Enomoto, Kyoko Inagaki-Ohara
Obesity increases the risk for gastric cancers. However, the occurrence and mechanisms of precancerous atrophic gastritis induced by high-fat diet (HFD) remain unclear. Here, we show that HFD-associated lipotoxicity induces precancerous lesions that are accompanied by the disruption of organelle homeostasis, tissue integrity, and deregulated expression of stemness genes in the gastric epithelium mediated by leptin receptor (ObR) signaling. Following HFD feeding, ectopic fat accumulated and expression of LAMP2A in lysosome and COX IV in mitochondria increased in the gastric mucosa...
September 28, 2016: Archives of Biochemistry and Biophysics
Sophie Wecht, Mauricio Rojas
Mesenchymal stem cells (MSCs) are a populace of non-haematopoietic multipotent stromal cells, which have the ability to differentiate into tissue derived from a single germ layer. MSCs have been isolated from various sites, including adipose tissue, skeletal muscle, synovium, spleen, thymus, lung and amniotic fluid, but are most often isolated from bone marrow. MSCs have several valuable functions that make them a promising therapeutic option in the field of regenerative medicine, including the secretion of anti-inflammatory cytokines and growth factors, the migration of cells to the site of injury when administered and the ability to 'rescue' cells through the transfer of functional mitochondria...
November 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
Attila Szabo, Attila Kovacs, Jordi Riba, Srdjan Djurovic, Eva Rajnavolgyi, Ede Frecska
N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins...
2016: Frontiers in Neuroscience
Claudia R Oliva, Tahireh Markert, Larry J Ross, E Lucile White, Lynn Rasmussen, Wei Zhang, Maaike Everts, Douglas R Moellering, Shannon M Bailey, Mark J Suto, Corinne E Griguer
The enzyme cytochrome c oxidase (CcO), or complex IV (EC, is a large transmembrane protein complex that serves as the last enzyme in the respiratory electron transport chain of eukaryotic mitochondria. CcO promotes the switch from glycolytic to oxidative phosphorylation (OXPHOS) metabolism and has been associated with increased self-renewal characteristics in gliomas. Increased CcO activity in tumors has been associated with tumor progression after chemotherapy failure, and patients with primary glioblastoma multiforme and high tumor CcO activity have worse clinical outcomes than those with low tumor CcO activity...
September 27, 2016: Journal of Biological Chemistry
Du Fang, Yu Qing, Shijun Yan, Doris Chen, Shirley ShiDu Yan
Mitochondria are critical to neurogenesis, but the mechanisms of mitochondria in neurogenesis have not been well explored. We fully characterized mitochondrial alterations and function in relation to the development of human induced pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neurons. Following directed differentiation of hiPSCs to DA neurons, mitochondria in these neurons exhibit pronounced changes during differentiation, including mature neurophysiology characterization and functional synaptic network formation...
October 11, 2016: Stem Cell Reports
Goodwin G Jinesh, Sharada Mokkapati, Keyi Zhu, Edwin E Morales
Pim kinases are being implicated in oncogenic process in various human cancers. Pim kinases primarily deal with three broad categories of functions such as tumorigenesis, protecting cells from apoptotic signals and evading immune attacks. Here in this review, we discuss the regulation of Pim kinases and their expression, and how these kinases defend cancer cells from therapeutic and immune attacks with special emphasis on how Pim kinases maintain their own expression during apoptosis and cellular transformation, defend mitochondria during apoptosis, defend cancer cells from immune attack, defend cancer cells from therapeutic attack, choose localization, self-regulation, activation of oncogenic transcription, metabolic regulation and so on...
November 2016: Apoptosis: An International Journal on Programmed Cell Death
Lauren D Van Wassenhove, Daria Mochly-Rosen, Kenneth I Weinberg
Maintenance of the hematopoietic stem cell (HSC) compartment depends on the ability to metabolize exogenously and endogenously generated toxins, and to repair cellular damage caused by such toxins. Reactive aldehydes have been demonstrated to cause specific genotoxic injury, namely DNA interstrand cross-links. Aldehyde dehydrogenase 2 (ALDH2) is a member of a 19 isoenzyme ALDH family with different substrate specificities, subcellular localization, and patterns of expression. ALDH2 is localized in mitochondria and is essential for the metabolism of acetaldehyde, thereby placing it directly downstream of ethanol metabolism...
September 2016: Molecular Genetics and Metabolism
Mijung Lee, Jae-Jun Ban, Ki Yoon Kim, Gye Sun Jeon, Wooseok Im, Jung-Joon Sung, Manho Kim
Amyotrophic lateral sclerosis (ALS) is a degenerative disorder that involves the death of motor neurons in the cortex, brain stem, and spinal cord. Adipose-derived stem cells (ADSCs) are considered as a perspective remedy for therapy of neurodegenerative diseases including ALS. Stem cells secrete various factors which can modulate a hostile environment, called paracrine effect. Exosomes are small extracellular vesicles containing cell derived factors and mediate paracrine effect of cells. Thus, exosomes from ADSCs (ADSC-exo) can be a potential candidate of therapeutic effects of stem cells...
October 21, 2016: Biochemical and Biophysical Research Communications
Yuelin Zhang, Zhendong Yu, Dan Jiang, Xiaoting Liang, Songyan Liao, Zhao Zhang, Wensheng Yue, Xiang Li, Sin-Ming Chiu, Yuet-Hung Chai, Yingmin Liang, Yenyen Chow, Shuo Han, Aimin Xu, Hung-Fat Tse, Qizhou Lian
Mesenchymal stem cells (MSCs) can donate mitochondria and rescue anthracycline-induced cardiomyocyte (CM) damage, although the underlying mechanisms remain elusive. We determined that the superior efficiency of mitochondrial transfer by human induced-pluripotent-stem-cell-derived MSCs (iPSC-MSCs) compared with bone marrow-derived MSCs (BM-MSCs) is due to high expression of intrinsic Rho GTPase 1 (MIRO1). Further, due to a higher level of TNFαIP2 expression, iPSC-MSCs are more responsive to tumor necrosis factor alpha (TNF-α)-induced tunneling nanotube (TNT) formation for mitochondrial transfer to CMs, which is regulated via the TNF-α/NF-κB/TNFαIP2 signaling pathway...
October 11, 2016: Stem Cell Reports
Sun Young Chung, Sarah Kishinevsky, Joseph R Mazzulli, John Graziotto, Ana Mrejeru, Eugene V Mosharov, Lesly Puspita, Parvin Valiulahi, David Sulzer, Teresa A Milner, Tony Taldone, Dimitri Krainc, Lorenz Studer, Jae-Won Shim
Parkinson's disease (PD) is characterized by the selective loss of dopamine neurons in the substantia nigra; however, the mechanism of neurodegeneration in PD remains unclear. A subset of familial PD is linked to mutations in PARK2 and PINK1, which lead to dysfunctional mitochondria-related proteins Parkin and PINK1, suggesting that pathways implicated in these monogenic forms could play a more general role in PD. We demonstrate that the identification of disease-related phenotypes in PD-patient-specific induced pluripotent stem cell (iPSC)-derived midbrain dopamine (mDA) neurons depends on the type of differentiation protocol utilized...
October 11, 2016: Stem Cell Reports
Krzysztof Marycz, Katarzyna Kornicka, Monika Marędziak, Paweł Golonka, Jakub Nicpoń
Adipose-derived mesenchymal stem cells (ASC) hold great promise in the treatment of many disorders including musculoskeletal system, cardiovascular and/or endocrine diseases. However, the cytophysiological condition of cells, used for engraftment seems to be fundamental factor that might determine the effectiveness of clinical therapy. In this study we investigated growth kinetics, senescence, accumulation of oxidative stress factors, mitochondrial biogenesis, autophagy and osteogenic differentiation potential of ASC isolated from horses suffered from equine metabolic syndrome (EMS)...
September 14, 2016: Journal of Cellular and Molecular Medicine
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