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Apoptotic secretome

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...
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
P Rademann, S Drechsler, M Kasiri, A Khadem, S Bahrami, H Ankersmit, M F Osuchowski
INTRODUCTION: Septic deaths occur in a deranged environment featuring both hyperinflammatory and immunosuppressive responses. At present, there is no approved immune-modulatory drug able to restore this imbalance. This study aimed to test a newly developed blood cell secretome preparation (APOSEC) upon outcome in the acute mouse model of polymicrobial sepsis. METHODS: 3-month-old female CD-1 mice (n = 40) underwent medium-severe cecal ligation and puncture (CLP) and were treated intraperitoneally with APOSEC (obtained from irradiated/apoptotic peripheral blood mononuclear cells) or saline at 6 h and 24 h post-CLP...
October 2015: Shock
C Penzenstadler, M Ashmwe, A Klotz, M Jafarmadar, M M Kasiri, H J Ankersmit, H Redl, S Bahrami
INTRODUCTION: Hemorrhagic traumatic shock (HTS) and reperfusion is often associated with general inflammatory response and organ dysfunction. Recent preclinical studies have shown that APOSEC exerts cytoprotective and/or immunomodulating effects. We evaluated the therapeutic potential of APOSEC in a HTS model in rats. METHODS: Rats were subjected to HTS (MAP 30-35 mmHg until decompensation) and a resuscitation protocol that includes a prehospital restrictive reperfusion (30 ml/kg/h, MAP maintained at 50-55 mmHg for 40 min) followed by an adequate reperfusion phase (75 ml/kg/h over 60 min, MAP to baseline)...
October 2015: Shock
Anna Labedz-Maslowska, Barbara Lipert, Dominika Berdecka, Sylwia Kedracka-Krok, Urszula Jankowska, Elzbieta Kamycka, Malgorzata Sekula, Zbigniew Madeja, Buddhadeb Dawn, Jolanta Jura, Ewa K Zuba-Surma
The current evidence suggests that beneficial effects of mesenchymal stem cells (MSCs) toward myocardial repair are largely due to paracrine actions of several factors. Although Monocyte chemoattractant protein-induced protein 1 (MCPIP1) is involved in the regulation of inflammatory response, apoptosis and angiogenesis, whether MCPIP1 plays any role in stem cell-induced cardiac repair has never been examined. By employing retroviral (RV)-transduced overexpression of MCPIP1, we investigated the impact of MCPIP1 on viability, apoptosis, proliferation, metabolic activity, proteome, secretome and differentiation capacity of murine bone marrow (BM) - derived MSCs...
2015: PloS One
Antonella Piscioneri, Sabrina Morelli, Maria Mele, Marcello Canonaco, Eleonora Bilotta, Pietro Pantano, Enrico Drioli, Loredana De Bartolo
UNLABELLED: In this work, we describe the development of a compartmentalized membrane system using neonatal rodent hippocampal cells and human mesenchymal stem cells (hMSCs) to investigate the neuroprotective effects of hMSCs. To elucidate this interaction an in vitro oxygen-glucose deprivation (OGD) model was used that mimics central nervous system insults in vivo. Cells were cultured in a membrane system with a sandwich configuration in which the hippocampal cells were seeded on a fluorocarbon (FC) membrane, and were separated by hMSCs through a semipermeable polyethersulfone (PES) membrane that ensures the transport of molecules and paracrine factors, but prevents cell-to-cell contact...
September 2015: Acta Biomaterialia
Thomas Haider, Romana Höftberger, Beate Rüger, Michael Mildner, Roland Blumer, Andreas Mitterbauer, Tanja Buchacher, Camillo Sherif, Patrick Altmann, Heinz Redl, Christian Gabriel, Mariann Gyöngyösi, Michael B Fischer, Gert Lubec, Hendrik Jan Ankersmit
After spinal cord injury (SCI), secondary damage caused by oxidative stress, inflammation, and ischemia leads to neurological deterioration. In recent years, therapeutic approaches to trauma have focused on modulating this secondary cascade. There is increasing evidence that the success of cell-based SCI therapy is due mainly to secreted factors rather than to cell implantation per se. This study investigated peripheral blood mononuclear cells as a source of factors for secretome- (MNC-secretome-) based therapy...
May 2015: Experimental Neurology
Fatemeh Amiri, Ali Jahanian-Najafabadi, Mehryar Habibi Roudkenar
Mesenchymal stem cells (MSCs) are under intensive investigation for use in cell-based therapies because their differentiation abilities, immunomodulatory effects, and homing properties offer potential for significantly augmenting regenerative capacity of many tissues. Nevertheless, major impediments to their therapeutic application, such as low proliferation and survival rates remain as obstacles to broad clinical use of MSCs. Another major challenge to evolution of MSC-based therapies is functional degradation of these cells as a result of their exposure to oxidative stressors during isolation...
March 2015: Cell Stress & Chaperones
Patrick Altmann, Michael Mildner, Thomas Haider, Denise Traxler, Lucian Beer, Robin Ristl, Bahar Golabi, Christian Gabriel, Fritz Leutmezer, Hendrik Jan Ankersmit
The pursuit of targeting multiple pathways in the ischemic cascade of cerebral stroke is a promising treatment option. We examined the regenerative potential of conditioned medium derived from rat and human apoptotic mononuclear cells (MNC), rMNC (apo sec) and hMNC (apo sec), in experimental stroke. We performed middle cerebral artery occlusion on Wistar rats and administered apoptotic MNC-secretomes intraperitoneally in two experimental settings. Ischemic lesion volumes were determined 48 hours after cerebral ischemia...
2014: F1000Research
Vladimir N Ivanov, Tom K Hei
Ionizing radiation alone or in combination with chemotherapy is the main treatment modality for brain tumors including glioblastoma. Adult neurons and astrocytes demonstrate substantial radioresistance; in contrast, human neural stem cells (NSC) are highly sensitive to radiation via induction of apoptosis. Irradiation of tumor cells has the potential risk of affecting the viability and function of NSC. In this study, we have evaluated the effects of irradiated glioblastoma cells on viability, proliferation and differentiation potential of non-irradiated (bystander) NSC through radiation-induced signaling cascades...
December 2014: Apoptosis: An International Journal on Programmed Cell Death
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