scholarly journals Osteogenic Effect and Cell Signaling Activation of Extremely Low-Frequency Pulsed Electromagnetic Fields in Adipose-Derived Mesenchymal Stromal Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Patrina S. P. Poh ◽  
Claudine Seeliger ◽  
Marina Unger ◽  
Karsten Falldorf ◽  
Elizabeth R. Balmayor ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Low Frequency ◽  
Alizarin Red ◽  
Intracellular Signaling Pathway ◽  
Extremely Low Frequency ◽  
Pulsed Electromagnetic

Extremely low-frequency pulsed electromagnetic field (ELF-PEMF) devices have been used in the clinic for the treatment of bone disorders over the past 30 years. However, the underlying mechanism of which ELF-PEMFs exert an effect on tissues at a cellular level is not well understood. Hence, in this study, we explored the potential of different ELF-PEMF signals in modulating human adipose-derived mesenchymal stromal cells’ (hAMSC) osteogenic capability. The cell proliferation rate was assessed using carboxyfluorescein succinimidyl ester (CFSE) method. The osteogenesis potential of cells was determined by alkaline phosphatase (ALP) activity, Alizarin-Red S staining, and RT-qPCR. Finally, the intracellular signaling pathway of a selected ELF-PEMF signal was examined using the PathScan Intracellular Signaling Array. Among the tested ELF-PEMF signals, program 20 (26 Hz) showed activation of the Akt and MAPK/ERK signaling cascade and significant upregulations of collagen I, alkaline phosphatase, and osteocalcin when compared to nonstimulated cells. This study demonstrates the potential of certain ELF-PEMF signal parameters to induce osteogenic differentiation of hAMSC and provides important clues in terms of the molecular mechanisms for the stimulation of osteogenic effects by ELF-PEMF on hAMSC.

scholarly journals Immunomodulatory effects of interferon-γ on human fetal cardiac mesenchymal stromal cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Karl-Henrik Grinnemo ◽  
Marie Löfling ◽  
Lubov Nathanson ◽  
Roland Baumgartner ◽  
Daniel F. J. Ketelhuth ◽  
...  
Keyword(s):  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
T Cell Activation ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
First Trimester ◽  
Interferon Γ ◽  
Systematic Evaluation ◽  
Immunomodulatory Effects ◽  
Functional Changes

Abstract Background Mesenchymal stromal cells (MSCs), due to their regenerative and immunomodulatory properties, are therapeutically used for diseases, including heart failure. As early gestational-phase embryonic tissues exhibit extraordinary regenerative potential, fetal MSCs exposed to inflammation offer a unique opportunity to evaluate molecular mechanisms underlying preferential healing, and investigate their inherent abilities to communicate with the immune system during development. The principal aim of this study was to evaluate the effects of interferon-γ (IFNγ) on the immunomodulatory effects of first-trimester human fetal cardiac (hfc)-MSCs. Methods hfcMSCs (gestational week 8) were exposed to IFNγ, with subsequent analysis of the whole transcriptome, based on RNA sequencing. Exploration of surface-expressed immunoregulatory mediators and modulation of T cell responses were performed by flow cytometry. Presence and activity of soluble mediators were assessed by ELISA or high-performance liquid chromatography. Results Stimulation of hfcMSCs with IFNγ revealed significant transcriptional changes, particularly in respect to the expression of genes belonging to antigen presentation pathways, cell cycle control, and interferon signaling. Expression of immunomodulatory genes and associated functional changes, including indoleamine 2,3-dioxygenase activity, and regulation of T cell activation and proliferation via programmed cell death protein (PD)-1 and its ligands PD-L1 and PD-L2, were significantly upregulated. These immunoregulatory molecules diminished rapidly upon withdrawal of inflammatory stimulus, indicating a high degree of plasticity by hfcMSCs. Conclusions To our knowledge, this is the first study performing a systematic evaluation of inflammatory responses and immunoregulatory properties of first-trimester cardiac tissue. In summary, our study demonstrates the dynamic responsiveness of hfcMSCs to inflammatory stimuli. Further understanding as to the immunoregulatory properties of hfcMSCs may be of benefit in the development of novel stromal cell therapeutics for cardiovascular disease.

scholarly journals Translational Insights into Extremely Low Frequency Pulsed Electromagnetic Fields (ELF-PEMFs) for Bone Regeneration after Trauma and Orthopedic Surgery

2019 ◽  
Vol 8 (12) ◽  
pp. 2028 ◽  
Author(s):  
Sabrina Ehnert ◽  
Steffen Schröter ◽  
Romina H. Aspera-Werz ◽  
Wiebke Eisler ◽  
Karsten Falldorf ◽  
...  
Keyword(s):  
Treatment Regimen ◽  
Electromagnetic Fields ◽  
Electrical Potential ◽  
Low Frequency ◽  
Treatment Modalities ◽  
Pulsed Electromagnetic Fields ◽  
Osteochondral Defects ◽  
Extremely Low Frequency ◽  
Pulsed Electromagnetic ◽  
Pemf Treatment

The finding that alterations in electrical potential play an important role in the mechanical stimulation of the bone provoked hype that noninvasive extremely low frequency pulsed electromagnetic fields (ELF-PEMF) can be used to support healing of bone and osteochondral defects. This resulted in the development of many ELF-PEMF devices for clinical use. Due to the resulting diversity of the ELF-PEMF characteristics regarding treatment regimen, and reported results, exposure to ELF-PEMFs is generally not among the guidelines to treat bone and osteochondral defects. Notwithstanding, here we show that there is strong evidence for ELF-PEMF treatment. We give a short, confined overview of in vitro studies investigating effects of ELF-PEMF treatment on bone cells, highlighting likely mechanisms. Subsequently, we summarize prospective and blinded studies, investigating the effect of ELF-PEMF treatment on acute bone fractures and bone fracture non-unions, osteotomies, spinal fusion, osteoporosis, and osteoarthritis. Although these studies favor the use of ELF-PEMF treatment, they likewise demonstrate the need for more defined and better controlled/monitored treatment modalities. However, to establish indication-oriented treatment regimen, profound knowledge of the underlying mechanisms in the sense of cellular pathways/events triggered is required, highlighting the need for more systematic studies to unravel optimal treatment conditions.

scholarly journals Immunomodulatory Effects of Mesenchymal Stromal Cells in Crohn’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ilse Molendijk ◽  
Marjolijn Duijvestein ◽  
Andrea E. van der Meulen-de Jong ◽  
Welmoed K. van Deen ◽  
Marloes Swets ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Perianal Fistulas ◽  
Allogeneic Mscs ◽  
New Treatment ◽  
Oxide Synthase ◽  
Phase I And Ii

The ability of mesenchymal stromal cells (MSCs) to suppress immune responses combined with their potential to actively participate in tissue repair provides a strong rationale for the use of MSCs as a new treatment option in diseases characterized by inflammation and severe tissue damage, such as Crohn’s disease (CD) and perianal fistulas. Multiple studies have shown that MSCs suppress a range of immune cells, such as dendritic cells (DC), naïve and effector T cells, and natural killer (NK) cells. Recently published papers attribute the immunosuppressive capacity of MSCs to soluble factors produced by MSCs, such as prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), and indoleamine 2,3-dioxygenase (IDO). Promising results are obtained from phase I and II clinical trials with autologous and allogeneic MSCs as treatment for refractory CD and perianal fistulas; however the question remains: what are the molecular mechanisms underlying the immunomodulating properties of MSCs? This paper highlights the present knowledge on the immunosuppressive effects of MSCs and its complexity in relation to CD and perianal fistulas.

scholarly journals The Role of Prep1 in the Regulation of Mesenchymal Stromal Cells

2019 ◽  
Vol 20 (15) ◽  
pp. 3639 ◽  
Author(s):  
Giorgia Maroni ◽  
Daniele Panetta ◽  
Raffaele Luongo ◽  
Indira Krishnan ◽  
Federica La Rosa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Fate ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Gene Dosage ◽  
Homeobox Gene ◽  
Fate Decision

Molecular mechanisms governing cell fate decision events in bone marrow mesenchymal stromal cells (MSC) are still poorly understood. Herein, we investigated the homeobox gene Prep1 as a candidate regulatory molecule, by adopting Prep1 hypomorphic mice as a model to investigate the effects of Prep1 downregulation, using in vitro and in vivo assays, including the innovative single cell RNA sequencing technology. Taken together, our findings indicate that low levels of Prep1 are associated to enhanced adipogenesis and a concomitant reduced osteogenesis in the bone marrow, suggesting Prep1 as a potential regulator of the adipo-osteogenic differentiation of mesenchymal stromal cells. Furthermore, our data suggest that in vivo decreased Prep1 gene dosage favors a pro-adipogenic phenotype and induces a “browning” effect in all fat tissues.

Role Of Long Pentraxin 3 (PTX3) In Wound Closure Induced By Bone Marrow-Derived Mesenchymal Stromal Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1220-1220
Author(s):  
Claudia Cappuzzello ◽  
Andrea Doni ◽  
Erica Dander ◽  
Fabio Pasqualini ◽  
Manuela Nebuloni ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Wound Closure ◽  
Conflicts Of Interest ◽  
Histological Evaluation ◽  
Pentraxin 3 ◽  
Alizarin Red ◽  
Matrix Deposition

Abstract Although several studies have shown the capacity of mesenchymal stromal cells (MSCs) to repair and regenerate different tissues, the mechanisms underlying these processes are not understood. Long Pentraxin 3 (PTX3) is a multifunctional protein produced by MSCs and other cell subsets upon activation with inflammatory cytokines. PTX3 is involved in innate immunity, inflammation and extracellular matrix deposition. In the present study we analyzed the potential role of PTX3 in wound repair process induced by MSCs. PTX3 knockout MSCs (PTX3-/-MSCs) were collected from bone marrow of PTX3-/- mice. After 3-5 culture passages the expression of surface markers was analyzed by flow cytometry and their osteogenic and adipogenic differentiation capacity was detected by alizarin red O and oil red S staining, respectively. The ability of PTX3-/-MSCs to abrogate T cell proliferation was evaluated by co-culturing MSCs and PBMCs previously activated with Phytohaemagglutinin. Finally, equal number of both PTX3-/-MSCs and wild type (WT) MSCs were implanted into excisional wounds created by a biopsy punch on the back of allogenic WT and PTX3-/- mice. Wound area was measured up to 14 day and calculated using an image analysis program. The wound specimens were collected at 2, 7 and 14 days and processed for histological analysis. We demonstrated that PTX3-/-MSCs, similarly to WT MSCs, displayed typical fibroblastoid morphology, they expressed common MSC markers and were able to differentiate into adipocytes and osteoblasts. In addition, they drastically decreased the mitogen-induced proliferation of lymphocyte. Importantly, in a mouse model of wound healing, PTX3-/- MSCs showed a highly significant defect in wound closure compared to WT MSCs at each time point. Histological evaluation of skin samples treated with PTX3-/- MSCs showed a reduction of the granulation tissue and a significant increase of neutrophils (GR-1+) in the wound bed. Moreover, wounds treated with PTX3-/- MSCs were characterized by an excessive accumulation of fibrin at the 2nd day after injury. Accordingly, PTX3-/- MSCs showed a defective ability to degrade the fibrin matrix in vitro. Finally, PTX3-/- MSCs failed to close the ulcers in PTX3-/- mice. In conclusion, we demonstrated that PTX3 deficiency does not alter the phenotype and the capacity of MSCs to differentiate into mesengetic lineages; however, the production of PTX3 represents an essential requirement for MSC ability of enhancing tissue repair. Disclosures: No relevant conflicts of interest to declare.

Effects of extremely low-frequency pulsed electromagnetic fields (ELF-PEMFs) on glioblastoma cells (U87)

2016 ◽  
Vol 36 (3) ◽  
pp. 238-247 ◽  
Author(s):  
Zeinab Akbarnejad ◽  
Hossein Eskandary ◽  
Cristian Vergallo ◽  
Seyed Noureddin Nematollahi-Mahani ◽  
Luciana Dini ◽  
...  
Keyword(s):  
Electromagnetic Fields ◽  
Low Frequency ◽  
Pulsed Electromagnetic Fields ◽  
Glioblastoma Cells ◽  
Extremely Low Frequency ◽  
Pulsed Electromagnetic
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