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Apoptotic secretome

A Srivastava, S Singh, C S Rajpurohit, P Srivastava, A Pandey, D Kumar, V K Khanna, A B Pant
A perturbed cellular homeostasis is a key factor associated with xenobiotic exposure resulting in various ailments. The local cellular microenvironment enriched with secretory components aids in cell-cell communication that restores this homeostasis. Deciphering the underlying mechanism behind this restorative potential of secretome could serve as a possible solution to many health hazards. We, therefore, explored the protective efficacy of the secretome of differentiated PC12 cells with emphasis on induction of autophagy and mitochondrial biogenesis...
March 30, 2018: Neuromolecular Medicine
Jeng-Ting Chen, Chien-Chun Liu, Jau-Song Yu, Hung-Hsuan Li, Ming-Chih Lai
Hypoxia is associated with poor prognosis in most solid tumors due to its multiple effects on therapy resistance, angiogenesis, apoptotic resistance, and tumor invasion/metastasis. Here we used a comprehensive omics profiling to investigate hypoxia-regulated gene expression in HCT116 colon cancer cells. Quantitative analyses of proteome and secretome were performed in HCT116 cells cultured under hypoxic or normoxic conditions. A total of 5700 proteins were quantified in proteome analysis and 722 proteins were quantified in secretome analysis...
March 7, 2018: Journal of Proteomics
Simona di Martino, Carla Azzurra Amoreo, Barbara Nuvoli, Rossella Galati, Sabrina Strano, Francesco Facciolo, Gabriele Alessandrini, Harvey I Pass, Gennaro Ciliberto, Giovanni Blandino, Ruggero De Maria, Mario Cioce
Adaptive resistance to therapy is a hallmark of cancer progression. To date, it is not entirely clear how microenvironmental stimuli would mediate emergence of therapy-resistant cell subpopulations, although a rearrangement of the cancer cell secretome following therapy-induced stress can be pivotal for such a process. Here, by using the highly chemoresistant malignant pleural mesothelioma (MPM) as an experimental model, we unveiled a key contribution of the chaperone HSP90 at assisting a chemotherapy-instigated Senescence-Associated-Secretory-Phenotype (SASP)...
March 2018: Oncogene
Denis Dufrane
Bone nonunion is a pathological condition in which all bone healing processes have stopped, resulting in abnormal mobility between 2 bone segments. The incidence of bone-related injuries will increase in an aging population, leading to such injuries reaching epidemic proportions. Tissue engineering and cell therapy using mesenchymal stem cells (MSCs) have raised the possibility of implanting living tissue for bone reconstruction. Bone marrow was first proposed as the source of stem cells for bone regeneration...
September 2017: Cell Transplantation
Sabrina Giacoppo, Soundara Rajan Thangavelu, Francesca Diomede, Placido Bramanti, Pio Conti, Oriana Trubiani, Emanuela Mazzon
Recent research has widely investigated the anti-inflammatory effects of mesenchymal stem cells and their secretory products, termed the secretome, in the treatment of multiple sclerosis (MS). The present study examined the capacity of the conditioned medium (CM) from human periodontal ligament stem cells (hPLSCs) under hypoxia (H-hPDLSCs-CM) to suppress experimental autoimmune encephalomyelitis (EAE), a murine model of MS. To induce EAE, female C57BL/6 mice were immunized with myelin oligodendroglial glycoprotein peptide35-55 At the onset of symptoms, H-hPDLSCs-CM was infused via the tail vein of mice...
December 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Elisabeth Simader, Denise Traxler, Mohammad Mahdi Kasiri, Helmut Hofbauer, Michael Wolzt, Christoph Glogner, Angela Storka, Michael Mildner, Ghazaleh Gouya, Alexandra Geusau, Carola Fuchs, Claudia Eder, Alexandra Graf, Michaela Schaden, Bahar Golabi, Marie-Bernadette Aretin, Susanne Suessner, Christian Gabriel, Walter Klepetko, Erwin Tschachler, Hendrik Jan Ankersmit
Developing effective therapies against chronic wound healing deficiencies is a global priority. Thus we evaluated the safety of two different doses of topically administered autologous APOSEC, the secretome of apoptotic peripheral blood mononuclear cells (PBMCs), in healthy male volunteers with artificial dermal wounds. Ten healthy men were enrolled in a single-center, randomized, double-blinded, placebo-controlled phase 1 trial. Two artificial wounds at the upper arm were generated using a 4-mm punch biopsy...
July 24, 2017: Scientific Reports
Taral R Lunavat, Lesley Cheng, Berglind O Einarsdottir, Roger Olofsson Bagge, Somsundar Veppil Muralidharan, Robyn A Sharples, Cecilia Lässer, Yong Song Gho, Andrew F Hill, Jonas A Nilsson, Jan Lötvall
The BRAF inhibitors vemurafenib and dabrafenib can be used to treat patients with metastatic melanomas harboring BRAF V600 mutations. Initial antitumoral responses are often seen, but drug-resistant clones with reactivation of the MEK-ERK pathway soon appear. Recently, the secretome of tumor-derived extracellular vesicles (EVs) has been ascribed important functions in cancers. To elucidate the possible functions of EVs in BRAF -mutant melanoma, we determined the RNA content of the EVs, including apoptotic bodies, microvesicles, and exosomes, released from such cancer cells after vemurafenib treatment...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
Naoko Ohtani
Cellular senescence is a state of irreversible cell proliferation arrest provoked by a persistent DNA damage induced by a variety of potentially oncogenic signals, and it functions as a primary tumor-suppression mechanism. Recent studies, however, revealed that senescent cells have the potential to secrete numerous inflammatory cytokines, chemokines, growth factors and matrix-remodeling factors, since unlike apoptotic cells, senescent cells are viable for a long period of time. This newly identified phenotype of cellular senescence, called senescence-associated secretory phenotype(SASP or senescence-associated secretome), could potentially provide beneficial effects, such as tissue repair, but sometimes could induce deleterious side effects, such as cancer progression, depending on the biological context...
2017: Clinical Calcium
Sowmya A Castro, Russell Collighan, Peter A Lambert, Irundika Hk Dias, Parbata Chauhan, Charlotte E Bland, Ivana Milic, Michael R Milward, Paul R Cooper, Andrew Devitt
Periodontal disease is a prevalent chronic inflammatory condition characterised by an aberrant host response to a pathogenic plaque biofilm resulting in local tissue damage and frustrated healing that can result in tooth loss. Cysteine proteases (gingipains) from the key periodontal pathogen Porphyromonas gingivalis have been implicated in periodontal disease pathogenesis by inhibiting inflammation resolution and are linked with systemic chronic inflammatory conditions such as rheumatoid arthritis. Efficient clearance of apoptotic cells is essential for the resolution of inflammation and tissue restoration...
March 2, 2017: Cell Death & Disease
Denis Dufrane
Bone non-union is a pathological condition in which all bone healing processes have stopped, resulting in abnormal mobility between two bone segments. The incidence of bone-related injuries will increase in an aging population, leading to such injuries reaching epidemic proportions. Tissue engineering and cell therapy using mesenchymal stem cells (MSCs) have raised the possibility of implanting living tissue for bone reconstruction. Bone marrow was first proposed as the source of stem cells for bone regeneration...
January 24, 2017: Cell Transplantation
Ioulia Vardaki, Claire Sanchez, Pedro Fonseca, Magnus Olsson, Dimitrios Chioureas, George Rassidakis, Anders Ullén, Boris Zhivotovsky, Magnus Björkholm, Theocharis Panaretakis
The intercellular crosstalk between hematological malignancies and the tumor microenvironment is mediated by cell-to-cell interactions and soluble factors. One component of the secretome that is gaining increasing attention is the extracellular vesicles and, in particular, the exosomes. Apart from the role as vectors of molecular information, exosomes have been shown to possess intrinsic biological activity. In this study, we found that caspase-3 is activated in L88 bone marrow stroma cell-derived exosomes and identified 1 of the substrates to be the antiapoptotic protein Bcl-xL...
December 8, 2016: Blood
Lucian Beer, Michael Mildner, Mariann Gyöngyösi, Hendrik Jan Ankersmit
For almost two decades, cell-based therapies have been tested in modern regenerative medicine to either replace or regenerate human cells, tissues, or organs and restore normal function. Secreted paracrine factors are increasingly accepted to exert beneficial biological effects that promote tissue regeneration. These factors are called the cell secretome and include a variety of proteins, lipids, microRNAs, and extracellular vesicles, such as exosomes and microparticles. The stem cell secretome has most commonly been investigated in pre-clinical settings...
December 2016: Apoptosis: An International Journal on Programmed Cell Death
Nermeen El-Moataz Bellah Ahmed, Masashi Murakami, Yujiro Hirose, Misako Nakashima
The secretome obtained from stem cell cultures contains an array of neurotrophic factors and cytokines that might have the potential to treat neurodegenerative conditions. Alzheimer's disease (AD) is one of the most common human late onset and sporadic neurodegenerative disorders. Here, we investigated the therapeutic potential of secretome derived from dental pulp stem cells (DPSCs) to reduce cytotoxicity and apoptosis caused by amyloid beta (Aβ) peptide. We determined whether DPSCs can secrete the Aβ-degrading enzyme, neprilysin (NEP), and evaluated the effects of NEP expression in vitro by quantitating Aβ-degrading activity...
2016: Stem Cells International
Stefan Hacker, Rainer Mittermayr, Stefanie Nickl, Thomas Haider, Diana Lebherz-Eichinger, Lucian Beer, Andreas Mitterbauer, Harald Leiss, Matthias Zimmermann, Thomas Schweiger, Claudia Keibl, Helmut Hofbauer, Christian Gabriel, Mariann Pavone-Gyöngyösi, Heinz Redl, Erwin Tschachler, Michael Mildner, Hendrik Jan Ankersmit
Burn wounds pose a serious threat to patients and often require surgical treatment. Skin grafting aims to achieve wound closure but requires a well-vascularized wound bed. The secretome of peripheral blood mononuclear cells (PBMCs) has been shown to improve wound healing and angiogenesis. We hypothesized that topical application of the PBMC secretome would improve the quality of regenerating skin, increase angiogenesis, and reduce scar formation after burn injury and skin grafting in a porcine model. Full-thickness burn injuries were created on the back of female pigs...
April 29, 2016: Scientific Reports
Chia-Hong Yeng, Pei-Jarn Chen, Hsiu-Kang Chang, Wei-Yu Lo, Chia-Chun Wu, Chia-Yu Chang, Chih-Ho Chou, Sheng-Hsien Chen
OBJECTIVE: Intravenous or intraspinal transplantation of human umbilical cord blood cells-derived CD34(+) cells (human CD34(+) cells) or mesenchymal stem cells after spinal cord injury (SCI) improved hind limb functional recovery in adult rats. The objective of this study is to ascertain whether SCI in rats can be attenuated by conditioned medium (CM) or secretome obtained from cultured human CD34(+) stem cells. MATERIALS AND METHODS: Sprague-Dawley rats were assigned to one of the following five groups: the sham group, the SCI group treated with vehicle solution (SCI + V), the SCI group treated with CM (SCI + CM), the SCI group treated with 17β-estradiol E2 (10 μg; SCI + E2), and the SCI group treated with CM plus E2 (SCI + CM + E2)...
February 2016: Taiwanese Journal of Obstetrics & Gynecology
Michael Horckmans, Larisa Ring, Johan Duchene, Donato Santovito, Maximilian J Schloss, Maik Drechsler, Christian Weber, Oliver Soehnlein, Sabine Steffens
AIMS: Acute myocardial infarction (MI) is the leading cause of mortality worldwide. Anti-inflammatory strategies to reduce neutrophil-driven acute post-MI injury have been shown to limit acute cardiac tissue damage. On the other hand, whether neutrophils are required for resolving post-MI inflammation and repair is unknown. METHODS AND RESULTS: We show that neutrophil-depleted mice subjected to MI had worsened cardiac function, increased fibrosis, and progressively developed heart failure...
February 2, 2016: European Heart Journal
Elma A O'Reilly, Luke Gubbins, Shiva Sharma, Riona Tully, Matthew Ho Zhing Guang, Karolina Weiner-Gorzel, John McCaffrey, Michele Harrison, Fiona Furlong, Malcolm Kell, Amanda McCann
BACKGROUND: Treatment options for women presenting with triple negative breast cancer (TNBC) are limited due to the lack of a therapeutic target and as a result, are managed with standard chemotherapy such as paclitaxel (Taxol®). Following chemotherapy, the ideal tumour response is apoptotic cell death. Post-chemotherapy, cells can maintain viability by undergoing viable cellular responses such as cellular senescence, generating secretomes which can directly enhance the malignant phenotype...
June 2015: BBA Clinical
Vijay Bhaskar Reddy Konala, Murali Krishna Mamidi, Ramesh Bhonde, Anjan Kumar Das, Radhika Pochampally, Rajarshi Pal
The unique properties of mesenchymal stromal/stem cells (MSCs) to self-renew and their multipotentiality have rendered them attractive to researchers and clinicians. In addition to the differentiation potential, the broad repertoire of secreted trophic factors (cytokines) exhibiting diverse functions such as immunomodulation, anti-inflammatory activity, angiogenesis and anti-apoptotic, commonly referred to as the MSC secretome, has gained immense attention in the past few years. There is enough evidence to show that the one important pathway by which MSCs participate in tissue repair and regeneration is through its secretome...
January 2016: Cytotherapy
Lucian Beer, Matthias Zimmermann, Andreas Mitterbauer, Adolf Ellinger, Florian Gruber, Marie-Sophie Narzt, Maria Zellner, Mariann Gyöngyösi, Sibylle Madlener, Elisabeth Simader, Christian Gabriel, Michael Mildner, Hendrik Jan Ankersmit
We previously showed that, when peripheral blood mononuclear cells (PBMCs) were stressed with ionizing radiation, they released paracrine factors that showed regenerative capacity in vitro and in vivo. This study aimed to characterize the secretome of PBMCs and to investigate its biologically active components in vitro and vivo. Bioinformatics analysis revealed that irradiated PBMCs differentially expressed genes that encoded secreted proteins. These genes were primarily involved in (a) pro-angiogenic and regenerative pathways and (b) the generation of oxidized phospholipids with known pro-angiogenic and inflammation-modulating properties...
November 16, 2015: Scientific Reports
Hye-Young An, Hyun-Soo Shin, Jeong-Seok Choi, Hun Jung Kim, Jae-Yol Lim, Young-Mo Kim
BACKGROUND AND PURPOSE: This study was conducted to determine whether a secretome from mesenchymal stem cells (MSC) modulated by hypoxic conditions to contain therapeutic factors contributes to salivary gland (SG) tissue remodeling and has the potential to improve irradiation (IR)-induced salivary hypofunction in a mouse model. MATERIALS AND METHODS: Human adipose mesenchymal stem cells (hAdMSC) were isolated, expanded, and exposed to hypoxic conditions (O2 < 5%)...
2015: PloS One
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