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Simone Vargas da Silva, Mariana Renovato-Martins, Cristiane Ribeiro-Pereira, Marta Citelli, Christina Barja-Fidalgo
OBJECTIVE: To investigate the role of obesity on the bone marrow microenvironment and evaluate its possible impact on the adipogenic potential of mesenchymal stem cells (MSC). METHODS: C57BL/6 male mice were fed with a high-fat diet (HFD) for 10 weeks. Femurs and tibiae were collected, and bone marrow mesenchymal stem cells (BM-MSC) were isolated and analyzed for proliferative potential, immunophenotype, and expression of adipogenesis markers. Their capacity to produce extracellular matrix proteins and proinflammatory cytokines in vitro was also evaluated...
October 18, 2016: Obesity
Somia H Abd Allah, Sally M Shalaby, Amal S El-Shal, Sameh M El Nabtety, Tarek Khamis, Shimaa A Abd El Rhman, Mahmoud A Ghareb, Hesham M Kelani
Exciting advances are revealing that breast milk harbors populations of stem and progenitor cells, and much attention is now intensified on delineating their properties and functions. The aim of this study is to isolate a mesenchymal stem cell (MSC)-like population from rabbit breast milk and track their integration into the different organs of the breastfed rabbits after taken by oral route and to explore the functional role of stem cells in the breastfed newborn babies. Ten newborn rabbits 2 weeks old fed on 2 × 10(6) PKH26-labeled rabbit milk derived-MSCs suspended in 2 mL Dulbecco's modified Eagle's medium (DMEM) and 10 newborn baby rabbits fed with 2 mL DMEM solution or with rabbit fibroblasts as a control group were used in the study...
October 17, 2016: IUBMB Life
Vasilina A Sergeeva, Svetlana V Kostyuk, Elizaveta S Ershova, Elena M Malinovskaya, Tatiana D Smirnova, Larisa V Kameneva, Natalia N Veiko
It has been established that cell-free DNA circulating in the bloodstream affects cells. The characteristics of cfDNA depend on the physiological state of the organism. As we showed previously, diseases can cause either GC-enrichment of the cell-free DNA pool or its oxidation. Thus, in cases of cerebral atherosclerosis, heart attack and rheumatic arthritis the cell-free DNA pool is GC-enriched and, in the case of cancer, both GC-enriched and oxidized. Herein we investigated the time-dependent effect of oxidized and GC-rich cell-free DNA on NF-kB and NRF2 signaling pathways in human mesenchymal stem cells and showed that they affect cells in different ways...
2016: Advances in Experimental Medicine and Biology
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
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
Anna Otte, Yuanyuan Yang, Juliane von der Ohe, Catharina Melzer, Peter Hillemanns, Friedrich Feuerhake, Ralf Hass
Chemotherapeutic drug testing of SCCOHT-1 and BIN-67 tumor cells revealed synergistic growth-inhibition of >95% in vitro with a combination of foretinib and FK228. Application of this drug combination in vivo in NODscid mice-induced SCCOHT-1GFP tumors was associated with ~6-fold reduction in tumor mass within 10 days, whereby synergistic effects of the two compounds remained undetectable compared to previous results with foretinib treatment alone. Histopathologic evaluation revealed a reduced vascularization and a lower amount of proliferating cells in the treated tumors...
October 14, 2016: International Journal of Oncology
Marie-Noëlle Labour, Mathieu Riffault, Søren T Christensen, David A Hoey
The recruitment of mesenchymal stem cells (MSCs) is a crucial process in the development, maintenance and repair of tissues throughout the body. Transforming growth factor-β1 (TGFβ1) is a potent chemokine essential for the recruitment of MSCs in bone, coupling the remodelling cycle. The primary cilium is a sensory organelle with important roles in bone and has been associated with cell migration and more recently TGFβ signalling. Dysregulation of TGFβ signalling or cilia has been linked to a number of skeletal pathologies...
October 17, 2016: Scientific Reports
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
Jenna N Harvestine, Nina L Vollmer, Steve S Ho, Christopher Andrew Zikry, Mark A Lee, J Kent Leach
Composite scaffolds of bioactive glass and poly(lactide-co-glycolide) provide advantages over homogenous scaffolds, yet their therapeutic potential can be improved by strategies that promote adhesion and present instructive cues to associated cells. Mesenchymal stem cell (MSC)-secreted extracellular matrix (ECM) enhances survival and function of associated cells. To synergize the benefits of an instructive ECM with composite scaffolds, we tested the capacity of ECM-coated composite scaffolds to promote cell persistence and resultant osteogenesis...
October 16, 2016: Biomacromolecules
Dae Young Yoo, Dae Won Kim, Jin Young Chung, Hyo Young Jung, Jong Whi Kim, Yeo Sung Yoon, In Koo Hwang, Jung Hoon Choi, Goang-Min Choi, Soo Young Choi, Seung Myung Moon
In the present study, we investigated the ability of Cu, Zn-superoxide dismutase (SOD1) to improve the therapeutic potential of adipose tissue-derived mesenchymal stem cells (Ad-MSCs) against ischemic damage in the spinal cord. Animals were divided into four groups: the control group, vehicle (PEP-1 peptide and artificial cerebrospinal fluid)-treated group, Ad-MSC alone group, and Ad-MSC-treated group with PEP-1-SOD1. The abdominal aorta of the rabbit was occluded for 30 min in the subrenal region to induce ischemic damage, and immediately after reperfusion, artificial cerebrospinal fluid or Ad-MSCs (2 × 10(5)) were administered intrathecally...
October 14, 2016: Neurochemical Research
A Burdzinska, B Dybowski, W Zarychta-Wisniewska, A Kulesza, R Zagozdzon, Z Gajewski, L Paczek
Cell therapy is emerging as an alternative treatment of stress urinary incontinence. However, many aspects of the procedure require further optimization. A large animal model is needed to reliably test cell delivery methods. In this study we aim to determine suitability of the goat as an experimental animal for testing intraurethral autologous cell transplantation in terms of urethral anatomy and cell culture parameters. The experiments were performed in 12 mature/aged female goats. Isolated caprine muscle derived cells (MDC) were myogenic in vitro and mesenchymal stem cells (MSC) population was able to differentiate into adipo-, osteo- and chondrogenic lineages...
October 14, 2016: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
Naoya Uchida, Juan J Haro-Mora, Atsushi Fujita, Duck-Yeon Lee, Thomas Winkler, Matthew M Hsieh, John F Tisdale
Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent an ideal source for in vitro modeling of erythropoiesis and a potential alternative source for red blood cell transfusions. However, iPS cell-derived erythroid cells predominantly produce ε- and γ-globin without β-globin production. We recently demonstrated that ES cell-derived sacs (ES sacs), known to express hemangioblast markers, allow for efficient erythroid cell generation with β-globin production. In this study, we generated several iPS cell lines derived from bone marrow stromal cells (MSCs) and peripheral blood erythroid progenitors (EPs) from sickle cell disease patients, and evaluated hematopoietic stem/progenitor cell (HSPC) generation after iPS sac induction as well as subsequent erythroid differentiation...
October 14, 2016: Stem Cells
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
Tsai-Jung Lu, Fang-Yao Chiu, Hsiao-Ying Chiu, Ming-Chau Chang, Shih-Chieh Hung
Articular cartilage has a very limited capacity for self-repair, and mesenchymal stem cells (MSCs) have the potential to treat cartilage defects and osteoarthritis. However, in-depth mechanistic studies regarding their applications are required. Here, we demonstrated the use of chitosan film culture for promoting chondrogenic differentiation of MSCs. We found that MSCs formed spheres two days after seeding on dishes coated with chitosan. When MSCs were induced in a chondrogenic induction medium on chitosan films, the size of spheres continuously increased for up to 21 days...
October 12, 2016: Cell Transplantation
Lei Hu, Ying Wen, Junji Xu, Tingting Wu, Chunmei Zhang, Jinsong Wang, Jie Du, Songlin Wang
Mesenchymal stem cell (MSC)-mediated bone regeneration is used to replace lost bone. However, methods to accelerate the process and stabilize regenerated bone remain limited. Therefore, we investigated the effect of bisphosphonates (BPs) on the function of bone marrow mesenchymal stem cells (BMMSCs) to determine if they might enhance MSC-mediated bone regeneration. We isolated and cultured BMMSCs from BALB/c mice and treated the cells with 0.1, 0.5, 1, 5, or 10 μM zoledronic acid (ZA; Zometa, a commercially available BP)...
October 13, 2016: Stem Cells and Development
Zahia Hamidouche, Karen Rother, Jens Przybilla, Axel Krinner, Denis Clay, Lydia Hopp, Claire Fabian, Alexandra Stolzing, Hans Binder, Pierre Charbord, Joerg Galle
The molecular mechanisms by which heterogeneity, a major characteristic of stem cells, is achieved are yet unclear. We here study the expression of the membrane stem cell antigen-1 (Sca-1) in mouse bone marrow Mesenchymal Stem Cell (MSC) clones. We show that subpopulations with varying Sca-1 expression profiles regenerate the Sca-1 profile of the mother population within a few days. However, after extensive replication in vitro the expression profiles shift to lower values and the regeneration time increases...
October 13, 2016: Stem Cells
Nisa Gul Amuk, Gökmen Kurt, Yusuf Baran, Volkan Seyrantepe, Melis Kartal Yandim, Aysun Adan, Secil Akyildiz Demir, Yagmur Kiraz, Mehmet Fatih Sonmez
AIM: The aim of this study is to evaluate and compare therapeutic effects of mesenchymal stem cell (MSCs) and osteoprotegerin (OPG) gene transfer applications on inhibition and/or repair of orthodontically induced inflammatory root resorption (OIIRR). MATERIALS AND METHODS: Thirty Wistar rats were divided into four groups as untreated group (negative control), treated with orthodontic appliance group (positive control), MSCs injection group, and OPG transfected MSCs [gene therapy (GT) group]...
October 12, 2016: European Journal of Orthodontics
Siddharth Shanbhag, Kamal Mustafa, Nikolaos Pandis, Jens R Nyengaard, Andreas Stavropoulos
The regenerative potential of tissue engineered bone constructs may be enhanced by in vitro co-culture and in vivo co-transplantation of vasculogenic and osteogenic (progenitor) cells. The objective of this study was to systematically review the literature to answer the focused question: in animal models, does co-transplantation of osteogenic and vasculogenic cells enhance bone regeneration in craniofacial defects, compared to solely osteogenic cell-seeded constructs? Following PRISMA guidelines, electronic databases were searched for controlled animal studies reporting co-transplantation of endothelial cells (EC) with mesenchymal stem cells (MSC) or osteoblasts (OB) in craniofacial critical-size bone defect (CSD) models...
October 12, 2016: Tissue Engineering. Part B, Reviews
Shanmugam Muruganandan, Rajgopal Govindarajan, Nichole M McMullen, Christopher J Sinal
Bone remodelling is a dynamic process requiring the coordinated action of formative (osteoblast) and resorptive (osteoclast) cell populations. An imbalance of the development and function of these cell types underlies several chronic bone loss disorders such as osteoporosis. Increased bone marrow adipocyte numbers commonly occur with bone loss disorders and numerous studies have documented an inverse relationship between bone marrow fat and bone formation. Osteoblasts and adipocytes derive in a competitive fashion from a common mesenchymal stem cell (MSC) precursor...
October 12, 2016: Stem Cells
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