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Mesenchymal stromal cell

Antonella Conforti, Nadia Starc, Simone Biagini, Luigi Tomao, Angela Pitisci, Mattia Algeri, Pietro Sirleto, Antonio Novelli, Giulia Grisendi, Olivia Candini, Cintia Carella, Massimo Dominici, Franco Locatelli, Maria Ester Bernardo
The risk of malignant transformation of ex-vivo expanded human mesenchymal stromal cells (huMSCs) has been debated in the last years; however, the biosafety of these cells after exposure to supramaximal physical and chemical stress has never been systematically investigated.We established an experimental in vitro model to induce supramaximal physical (ionizing radiation, IR) and chemical (starvation) stress on ex-vivo expanded bone marrow (BM)-derived huMSCs and investigated their propensity to undergo malignant transformation...
October 15, 2016: Oncotarget
Jana Jakubikova, Danka Cholujova, Teru Hideshima, Paulina Gronesova, Andrea Soltysova, Takeshi Harada, Jungnam Joo, Sun-Young Kong, Raphael E Szalat, Paul G Richardson, Nikhil C Munshi, David M Dorfman, Kenneth C Anderson
Specific niches within the tumor bone marrow (BM) microenvironment afford a sanctuary for multiple myeloma (MM) clones due to stromal cell-tumor cell interactions, which confer survival advantage and drug resistance. Defining the sequelae of tumor cell interactions within the MM niches on an individualized basis may provide the rationale for personalized therapies. To mimic the MM niche, we here describe a new 3D co-culture ex-vivo model in which primary MM patient BM cells are co-cultured with mesenchymal stem cells (MSC) in a hydrogel 3D system...
October 13, 2016: Oncotarget
Amanda Faria Assoni, Giuliana Castello, Marcos Valadares, Melinda Beccari, Juliana Gomes, Mayra Pelatti, Miguel Mitne-Neto, Valdemir Melechco Carvalho, Mayana Zatz
Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder caused by null mutations in the dystrophin gene. Although the primary defect is the deficiency of muscle dystrophin, secondary events, including chronic inflammation, fibrosis and muscle regeneration failure are thought to actively contribute to disease progression. Despite several advances, there is still no effective therapy for DMD. Therefore, the potential regenerative capacities, as well as immune-privileged properties of Mesenchymal Stromal Cells (MSCs), have been the focus of intense investigation in different animal models aiming the treatment of these disorders...
October 20, 2016: Stem Cells and Development
Natalya A Goloviznina, Santhosh Chakkaramakkil Verghese, Young Me Yoon, Oleh Taratula, Daniel L Marks, Peter Kurre
Mesenchymal stromal cells (MSC) present in the bone marrow (BM) microenvironment secrete cytokines and angiogenic factors that support the maintenance and regenerative expansion of hematopoietic stem and progenitor cells (HSPC). Here, we tested the hypothesis that extracellular vesicles (EVs) released by MSC contribute to the paracrine crosstalk that shapes hematopoietic function. We systematically characterized EV release by murine stromal cells and demonstrate that MSC-derived EVs prompt a loss of HSPC quiescence with concomitant expansion of murine myeloid progenitors...
October 7, 2016: Journal of Biological Chemistry
Katie Pollock, Guanglin Yu, Ralph Moller-Trane, Marissa Koran, Peter Dosa, David McKenna, Allison Hubel
There is demand for non-DMSO cryoprotective agents that maintain cell viability without causing poor post thaw function or systemic toxicity. The focus of this investigation involves expanding our understanding of multicomponent osmolyte solutions and their ability to preserve cell viability during freezing. Controlled cooling rate freezing, Raman microscopy, and differential scanning calorimetry (DSC) were utilized to evaluate the differences in recovery and ice crystal formation behavior for solutions containing multiple cryoprotectants including sugars, sugar alcohols, and small molecule additives...
October 19, 2016: Tissue Engineering. Part C, Methods
Andreas Svensson, Tania Ramos-Moreno, Sofia Eberstål, Stefan Scheding, Johan Bengzon
Gene profiling has revealed that malignant gliomas can be divided into four distinct molecular subtypes, where tumors with a mesenchymal gene expression are correlated with short survival. The present investigation was undertaken to clarify whether human malignant gliomas contain endogenous mesenchymal stromal cells (MSC), fulfilling consensus criteria defined by The International Society for Cellular Therapy, recruited from the host. We found that MSC-like cells can be isolated from primary human malignant gliomas...
October 18, 2016: Journal of Neuro-oncology
Ahmad Abu-Khader, Roya Pasha, Gwendoline C D Ward, Gavin Boisjoli, Nicolas Pineault
Engraftment outcomes are strongly correlated with the numbers of hematopoietic stem and progenitor cells (HSPC) infused. Expansion of umbilical cord blood (CB) HSPC has gained much interest lately since infusion of expanded HSPC can accelerate engraftment and improve clinical outcomes. Many novel protocols based on different expansion strategies of HSPC and their downstream derivatives are under development. Herein, we describe the production and properties of serum-free medium (SFM) conditioned with mesenchymal stromal cells derived-osteoblasts (OCM) for the expansion of umbilical CB cells and progenitors...
October 18, 2016: Cytotechnology
Elizabeth M Meier, Bin Wu, Aamir Siddiqui, Donna G Tepper, Michael T Longaker, Mai T Lam
: Efforts have been made to engineer knee meniscus tissue for injury repair, yet most attempts have been unsuccessful. Creating a cell source that resembles the complex, heterogeneous phenotype of the meniscus cell remains difficult. Stem cell differentiation has been investigated, mainly using bone marrow mesenchymal cells and biochemical means for differentiation, resulting in no solution. Mechanical stimulation has been investigated to an extent with no conclusion. Here, we explore the potential for and effectiveness of mechanical stimulation to induce the meniscal phenotype in adipose-derived stromal cells...
September 2016: Plastic and Reconstructive Surgery. Global Open
Cees van Kooten, Ton J Rabelink, Johan W de Fijter, Marlies E J Reinders
PURPOSE OF REVIEW: Progress in the improvement of short-term and long-term outcomes of kidney transplantation seems to have reached a plateau, partially due to consequences of very efficient, but nonspecific immunosuppressive drugs. In recent years, various forms of cell therapy, including the use of mesenchymal stromal cells, have been put forward as an alternative strategy for more defined therapy. It is thought that these therapies will not only allow controlled tapering of immunosuppressive medication, but might bring us also closer to the ambition of generating donor-specific immune regulation and tolerance...
October 15, 2016: Current Opinion in Organ Transplantation
Christian L Johnson, Yorick Soeder, Marc H Dahlke
PURPOSE OF REVIEW: The current review presents an update on the existing preclinical and human experience of mesenchymal stromal cell (MSC) therapies for post-transplant immunomodulation. RECENT FINDINGS: Although results from early clinical studies have demonstrated that the application of autologous and allogeneic MSC to be both safe and feasible in a solid organ transplantation setting, for example in liver, the efficacy of MSC immunotherapy demonstrated in preclinical models has yet to be replicated in human clinical trials...
October 7, 2016: Current Opinion in Organ Transplantation
Adriana Borriello, Ilaria Caldarelli, Debora Bencivenga, Emanuela Stampone, Silverio Perrotta, Adriana Oliva, Fulvio Della Ragione
The hope of selectively targeting cancer cells by therapy and eradicating definitively malignancies is based on the identification of pathways or metabolisms that clearly distinguish "normal" from "transformed" phenotypes. Some tyrosine kinase activities, specifically unregulated and potently activated in malignant cells, might represent important targets of therapy. Consequently, tyrosine kinase inhibitors (TKIs) might be thought as the "vanguard" of molecularly targeted therapy for human neoplasias. Imatinib and the successive generations of inhibitors of Bcr-Abl1 kinase, represent the major successful examples of TKI use in cancer treatment...
October 13, 2016: Oncotarget
Yaser Atlasi, Rubina Noori, Ivana Marolin, Patrick Franken, Joana Brandao, Katharina Biermann, Paola Collini, Mariam Grigorian, Eugene Lukanidin, Noona Ambartsumian, Riccardo Fodde
INTRODUCTION: S100a4 is a calcium-binding protein belonging to the family of S100-proteins, highly expressed in different stromal cell types. S100A4 has been reported as a prognostic marker in colorectal cancer in association with tumour progression and metastasis. METHODS: In this study, we analysed the in vivo role of S100a4 in intestinal tumour initiation and progression using different transgenic and knockout mouse models. RESULTS: We found that genetic ablation or overexpression of S100a4 in both Apc- and Smad4-mutant mice do not affect tumour initiation in the intestinal tract...
October 14, 2016: European Journal of Cancer
Bipradas Roy, Mary E Curtis, Letimicia S Fears, Samuel N Nahashon, Hugh M Fentress
Obesity and osteoporosis are two alarming health disorders prominent among middle and old age populations, and the numbers of those affected by these two disorders are increasing. It is estimated that more than 600 million adults are obese and over 200 million people have osteoporosis worldwide. Interestingly, both of these abnormalities share some common features including a genetic predisposition, and a common origin: bone marrow mesenchymal stromal cells. Obesity is characterized by the expression of leptin, adiponectin, interleukin 6 (IL-6), interleukin 10 (IL-10), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), macrophage colony stimulating factor (M-CSF), growth hormone (GH), parathyroid hormone (PTH), angiotensin II (Ang II), 5-hydroxy-tryptamine (5-HT), Advance glycation end products (AGE), and myostatin, which exert their effects by modulating the signaling pathways within bone and muscle...
2016: Frontiers in Physiology
Alena-Svenja Wagner, Kristina Glenske, Verena Wolf, Daniela Fietz, Sybille Mazurek, Thomas Hanke, Andreas Moritz, Stefan Arnhold, Sabine Wenisch
The effects of extracellular calcium on osteogenic differentiation capacity of human bone-derived mesenchymal stromal cells with special regard to connexin 43 (cx43) have been investigated by means of cell culture experiments. Mesenchymal stromal cells isolated from human cancellous bone were cultured on tissue culture plates at different calcium ion (Ca(2+)) concentrations (1.8mmoll(-1), 10mmoll(-1), 20mmoll(-1)). Cell responses were evaluated by quantitative RT-PCR, immunofluorescence staining, and Lucifer Yellow fluorescence uptake experiments...
October 13, 2016: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Dominique L Doster, Amanda R Jensen, Sina Khaneki, Troy A Markel
Intestinal ischemia is a devastating intraabdominal emergency that often necessitates surgical intervention. Mortality rates can be high, and patients who survive often have significant long-term morbidity. The implementation of traditional medical therapies to prevent or treat intestinal ischemia have been sparse over the last decade, and therefore, the use of novel therapies are becoming more prevalent. Cellular therapy using mesenchymal stromal cells is one such treatment modality that is attracting noteworthy attention in the scientific community...
October 10, 2016: Cytotherapy
Elizabeth K Sage, Ricky M Thakrar, Sam M Janes
The cell therapy industry has grown rapidly over the past 3 decades, and multiple clinical trials have been performed to date covering a wide range of diseases. The most frequently used cell is mesenchymal stromal cells (MSCs), which have been used largely for their anti-inflammatory actions and in situations of tissue repair and although they have demonstrated a good safety profile, their therapeutic efficacy has been limited. In addition to these characteristics MSCs are being used for their homing and engraftment properties and have been genetically modified to enable targeted delivery of a variety of therapeutic agents in both malignant and nonmalignant conditions...
November 2016: Cytotherapy
Hiroaki Kasashima, Masakazu Yashiro, Hirohisa Nakamae, Kisyu Kitayama, Go Masuda, Haruhito Kinoshita, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Takahiko Nakane, Masayuki Hino, Kosei Hirakawa, Masaichi Ohira
Tumor stromal cells play a critical role in the progression of diffuse-type gastric cancer (DGC). The aim of this study was to clarify where tumor stromal cells originate from and which factor(s) recruits them into the tumor stroma. Immunodeficient mice with bone marrow transplantation from the cytomegalovirus enhancer/chicken β-actin promoter-enhanced green fluorescent protein mice were used for the in vivo experiments. An in vitro study analyzed the chemotaxis-stimulating factor from DGC cells using bone marrow-derived mesenchymal cells (BM-MCs)...
October 8, 2016: American Journal of Pathology
Azadeh Esmaeli, Mojgan Moshrefi, Ali Shamsara, Seyed Hasan Eftekhar-Vaghefi, Seyed Noureddin Nematollahi-Mahani
BACKGROUND: Fetal bovine serum (FBS) is widely used in cell culture laboratories, risk of zoonotic infections and allergic side effects create obstacles for its use in clinical trials. Therefore, an alternative supplement with proper inherent growth-promoting activities is demanded. OBJECTIVE: To find FBS substitute, we tested human umbilical cord blood serum (hUCS) for proliferation of human umbilical cord matrix derived mesenchymal stem cells (hUC-MSCs) and human bone marrow-derived mesenchymal cells (hBM-MSCs)...
September 2016: International Journal of Reproductive Biomedicine (Yazd, Iran)
Bruno Sangiorgi, Rodrigo Alexandre Panepucci
In the last decade, the immunomodulatory properties of mesenchymal stromal cells (MSCs) have attracted a lot of attention, due to their potential applicability in the treatment of graft-versus-host disease (GVHD), a condition frequently associated with opportunistic infections. The present review addresses how Pathogen-Associated Molecular Patterns (PAMPS) modulate the immunosuppressive phenotype of human MSCs by signaling through Toll-like receptors (TLRs). Overall, we observed that regardless of the source tissue, human MSCs express TLR2, TLR3, TLR4, and TLR9...
2016: Stem Cells International
John H Saunders, David Onion, Pamela Collier, Matthew S Dorrington, Richard H Argent, Philip A Clarke, Alex M Reece-Smith, Simon L Parsons, Anna M Grabowska
BACKGROUND: A model to predict chemotherapy response would provide a marked clinical benefit, enabling tailored treatment of oesophageal cancer, where less than half of patients respond to the routinely administered chemotherapy. METHODS: Cancer cells were established from tumour biopsies taken from individual patients about to undergo neoadjuvant chemotherapy. A 3D-tumour growth assay (3D-TGA) was developed, in which cancer cells were grown with or without supporting mesenchymal cells, then subjected to chemo-sensitivity testing using the standard chemotherapy administered in clinic, and a novel emerging HDAC inhibitor, Panobinostat...
October 6, 2016: Oncotarget
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