Research > Stem Cells
Molecular and Cellular Effects of In Vitro Shockwave Treatment on Lymphatic Endothelial Cells - Extracorporeal shockwave treatment was shown to improve orthopaedic diseases and wound healing and to stimulate lymphangiogenesis in vivo. The aim of this study was to investigate in vitro shockwave treatment (IVSWT) effects on lymphatic endothelial cell (LEC) behavior and lymphangiogenesis. We analyzed migration,
proliferation, vascular tube forming capability and marker expression changes of LECs after IVSWT compared with HUVECs. Finally, transcriptome- and miRNA analyses were conducted to gain deeper insight into the IVSWT-induced molecular mechanisms in LECs. The results indicate that IVSWT-mediated proliferation changes of LECs are highly energy flux density-dependent and LEC 2D as well as 3D migration was enhanced through IVSWT. IVSWT suppressed HUVEC 3D migration but enhanced vasculogenesis. Furthermore, we identified podoplaninhigh and podoplaninlow cell subpopulations, whose ratios changed upon IVSWT treatment. Transcriptome- and miRNA analyses on these populations showed differences in genes specific for signaling and vascular tissue. Our findings help to understand the cellular and molecular mechanisms underlying shockwave-induced lymphangiogenesis in vivo. More..
miR-19a-3p containing exosomes improve function of ischaemic myocardium upon shock wave therapy - As many current approaches for heart regeneration exert unfavourable side effects, the induction of endogenous repair mechanisms in ischaemic heart disease is of particular interest. Recently, exosomes carrying angiogenic miRNAs have been described to improve heart function. However, it remains challenging to stimulate specific release of reparative exosomes in ischaemic myocardium. In the present study, we sought to test the hypothesis that the physical stimulus of shock wave therapy (SWT) causes the release of exosomes. We aimed to substantiate the pro-angiogenic impact of the released factors, to identify the nature of their cargo, and to test their efficacy in vivo supporting regeneration and recovery after myocardial ischaemia. More..
Improvement of adipose tissue–derived cells by low-energy extracorporeal shock wave therapy - Cell-based therapies with autologous adipose tissue–derived cells have shown great potential in several clinical studies in the last decades.The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency. More..
proliferation, vascular tube forming capability and marker expression changes of LECs after IVSWT compared with HUVECs. Finally, transcriptome- and miRNA analyses were conducted to gain deeper insight into the IVSWT-induced molecular mechanisms in LECs. The results indicate that IVSWT-mediated proliferation changes of LECs are highly energy flux density-dependent and LEC 2D as well as 3D migration was enhanced through IVSWT. IVSWT suppressed HUVEC 3D migration but enhanced vasculogenesis. Furthermore, we identified podoplaninhigh and podoplaninlow cell subpopulations, whose ratios changed upon IVSWT treatment. Transcriptome- and miRNA analyses on these populations showed differences in genes specific for signaling and vascular tissue. Our findings help to understand the cellular and molecular mechanisms underlying shockwave-induced lymphangiogenesis in vivo. More..
miR-19a-3p containing exosomes improve function of ischaemic myocardium upon shock wave therapy - As many current approaches for heart regeneration exert unfavourable side effects, the induction of endogenous repair mechanisms in ischaemic heart disease is of particular interest. Recently, exosomes carrying angiogenic miRNAs have been described to improve heart function. However, it remains challenging to stimulate specific release of reparative exosomes in ischaemic myocardium. In the present study, we sought to test the hypothesis that the physical stimulus of shock wave therapy (SWT) causes the release of exosomes. We aimed to substantiate the pro-angiogenic impact of the released factors, to identify the nature of their cargo, and to test their efficacy in vivo supporting regeneration and recovery after myocardial ischaemia. More..
Improvement of adipose tissue–derived cells by low-energy extracorporeal shock wave therapy - Cell-based therapies with autologous adipose tissue–derived cells have shown great potential in several clinical studies in the last decades.The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency. More..
Doubts over heart stem-cell therapy - The cells are then injected back into the patient, to help repair damaged tissue. Original claims that they differentiated into replacement cells have been rejected , and many clinicians now believe that the cells act by releasing molecules that cause inflammation, with an attendant growth of oxygen-delivering small blood vessels, in the damaged tissue. More..
Shock Wave Therapy Improves Cardiac Function in a Model of Chronic Ischemic Heart Failure: Evidence for a Mechanism Involving VEGF Signaling and the Extracellular Matrix - Background-—Mechanical stimulation of acute ischemic myocardium by shock wave therapy (SWT) is known to improve cardiac function by induction of angiogenesis. However, SWT in chronic heart failure is poorly understood. We aimed to study whether mechanical stimulation upon SWT improves heart function in chronic ischemic heart failure by induction of angiogenesis and postnatal vasculogenesis and to dissect underlying mechanisms. More.
Shock Wave Therapy Improves Cardiac Function in a Model of Chronic Ischemic Heart Failure: Evidence for a Mechanism Involving VEGF Signaling and the Extracellular Matrix - Background-—Mechanical stimulation of acute ischemic myocardium by shock wave therapy (SWT) is known to improve cardiac function by induction of angiogenesis. However, SWT in chronic heart failure is poorly understood. We aimed to study whether mechanical stimulation upon SWT improves heart function in chronic ischemic heart failure by induction of angiogenesis and postnatal vasculogenesis and to dissect underlying mechanisms. More.
Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis - (Jieyuan Zhang, Junjie Guan, Xin Niu, Guowen Hu, Shangchun Guo , Qing Li , Zongping Xie , Changqing Zhang and Yang Wang) - Human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) have emerged as a promising alternative for stem cell transplantation therapy. Exosomes derived from mesenchymal stem cells (MSC-Exos) can play important roles in repairing injured tissues. However, to date, no reports have demonstrated the use of hiPSC-MSC-Exos in cutaneous wound healing, and little is known regarding their underlying mechanisms in tissue repair. More..
MSC-derived exosomes ameliorate erectile dysfunction by alleviation of corpus cavernosum smooth muscle apoptosis in a
rat model of cavernous nerve injury - (Xi Ouyang , Xiaoyan Han , Zehong Chen, Jiafeng Fang, Xuna Huang and Hongbo Wei) - This study investigated the therapeutic effects of MSC-derived exosomes (MSC-Exos) on erectile function in a rat model of cavernous nerve injury (CNI). More..
rat model of cavernous nerve injury - (Xi Ouyang , Xiaoyan Han , Zehong Chen, Jiafeng Fang, Xuna Huang and Hongbo Wei) - This study investigated the therapeutic effects of MSC-derived exosomes (MSC-Exos) on erectile function in a rat model of cavernous nerve injury (CNI). More..
Cellular mechanotransduction: putting all the pieces together again - (Vascular Biology Program, Departments of Pathology and Surgery, Harvard Medical School and Children’s Hospital, Boston, Massachusetts, USA) - Analysis of cellular mechanotransduction, the mechanism by which cells convert mechanical signals into biochemical responses, has focused on identification of critical mechanosensitive molecules and cellular components. Stretch-activated ion channels, caveolae, integrins, cadherins, growth factor receptors, myosin motors, cytoskeletal filaments, nuclei, extracellular matrix, and numerous other structures and signaling molecules have all been shown to contribute to the mechanotransduction response. More..
Mesenchymal stem cells: Myths and reality - Mesenchymal stem cells (MSCs; also called mesenchymal stromal cells) have received much attention during the last two decades, at first because of their regeneration capacity and poor immunogenicity and, more recently, because of their proved immunomodulatory function. More..
Angiogenic response upon shock wave treatment of the ischaemic muscle - Shock wave therapy (SWT) represents a clinically widely used angiogenic and thus regenerative approach for the treatment of ischaemic heart or limb disease. Despite promising results in preclinical and clinical trials, the exact mechanism of action remains unknown. Toll-like receptor 3, which is part of the innate immunity, is activated by binding doublestranded (ds) RNA. It plays a key role in inflammation, a process that is needed also for angiogenesis. We hypothesize that SWT causes cellular cavitation without damaging the target cells, thus liberating cytoplasmic RNA that in turn activates TLR3. More..
Scientific Reports - Gene transfection by shock waves - Extracorporeal shock wave (SW) therapy has been studied in the transfection of naked nucleic acids into various cell lines through the process of sonoporation, a process that affects the permeation of cell membranes, which can be an effect of cavitation. In this study, siRNAs were efficiently transfected into primary cultured cells and mouse tumor tissue via SW treatment. Furthermore SWinduced siRNA transfection was not mediated by SW-induced sonoporation, but by microparticles (MPs) secreted from the cells. Interestingly, the transfection effect of the siRNAs was transferable through the secreted MPs from human umbilical vein endothelial cell (HUVEC) culture medium after treatment with SW, into HUVECs in another culture plate without SW treatment. In this study, we suggest for the first time a mechanism of gene transfection induced by low-energy SW through secreted MPs, and show that it is an efficient physical gene transfection method in vitro and represents a safe therapeutic strategy for site-specific gene delivery in vivo. More..
Improvement of adipose tissue–derived cells by low-energy extracorporeal shock wave therapy - Cell-based therapies with autologous adipose tissue–derived cells have shown great potential in several clinical studies in the last decades.The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue– derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency. More...
Novel Approach to Obtain an Activated Fat Graph - One of the mainstays of facial rejuvenation strategies is volume restoration, which can be achieved by autologous fat grafting. In our novel approach, we treated the adipose tissue harvest site with extracorporeal shock wave therapy (ESWT) in order to improve the quality of the regenerative cells in situ. The latter was demonstrated by characterizing the cells of the stromal vascular fraction (SVF) in the harvested liposuction material regarding cell yield, adenosine triphosphate (ATP) content, proliferative capacity, surface marker profile, differentiation potential and secretory protein profile More..
UGA In vitro study: ESWT treatment of platelets causes increased release of growth factors - Platelet-rich plasma (PRP) and extracorporeal shockwave therapy (ESWT) are both used for the treatment of soft tissue injuries in horses. Clinically, the question has been raised whether these two therapies could be used in combination. The hypothesis of this study was the application of ESWT to PRP would increase the release of platelet derived growth factors (PDGF) and transforming growth factors beta 1 (TGF) from platelets. More..
Shock wave treatment enhances cell proliferation and improves wound healing by ATP release-coupled extracellular signal-regulated kinase (ERK) activation - Shock wave treatment accelerates impaired wound healing in diverse clinical situations. However, the mechanisms underlying the beneficial effects of shock waves have not yet been fully revealed. Because cell proliferation is a major requirement in the wound healing cascade, we used in vitro studies and an in vivo wound healing model to study whether shock wave treatment influences proliferation by altering major extracellular factors and signaling pathways involved in cell proliferation More..
Original hypothesis: Extracorporeal shockwaves as a homeostatic autoimmune restorative treatment (HART) for Type 1 diabetes mellitus - Mononuclear invasion of Langerhans islet and the ensuing insulitis triggers signal-transduction for the autoimmune mediated pancreatic beta-cell (b-cell) apoptosis that severely disrupts insulin production resulting in hyperglycemia associated with Type-1 diabetes (T1DM). Today extensive global research is being conducted to eliminate the need for insulin, and even prevent or find a cure for T1DM More..
Shockwaves induce osteogenic differentiation of human mesenchymal stem cells through ATP release and activation of P2X7 receptors - Shockwave fractures treatment promotes bone healing of nonunion fractures. In this study, we investigated whether this effect could be due to adenosine 5’-triphosphate (ATP) release-induced differentiation of human mesenchymal stem cells (hMSCs) into osteoprogenitor cells. Cultured bone marrow-derived hMSCs were subjected to shockwave treatment and ATP release was assessed. Osteogenic differentiation and mineralization of hMSCs were evaluated by examining alkaline phosphatase activity, osteocalcin production, and calcium nodule formation. Expression of P2X7 receptors and c-fos and c-jun mRNA was determined with real-time reverse transcription polymerase chain reaction and Western blotting. P2X7-siRNA, apyrase, P2 receptor antagonists, and p38 MAPK inhibitors were used to evaluate the roles of ATP release, P2X7 receptors, and p38 MAPK sig naling in shockwave-induced osteogenic hMSCs differentiation More..
Cell biological effects of mechanical stimulations generated by focused extracorporeal shock wave applications on cultured human bone marrow stromal cells - Human bone marrow stromal cells (hBMSCs) bear tremendous clinical potential due to their immunomodulatory properties in transplantation settings and their contribution to tissue regeneration. In fact, they are among the most promising types of stem-like cells for therapeutic applications and are the subject of intense research. However, the clinical use of hBMSCs has been confounded by limitations in their availability; they are scarce cells cumbersome to isolate and purify. Additionally, they are difficult to target to the site of injury in regeneration experiments. In order to combat these limitations, focused extracorporeal shock waves (fESW, 0.2/0.3 mJ ∗ mm−2 ) were applied to purified, cultured hBMSCs. fESW (0.2 mJ ∗ mm−2 ) stimulations were found to increase hBMSCs' growth rate (p b 0.05), proliferation (p b 0.05), migration, cell tracking and wound healing (p b 0.05, respectively), as well as to reduce the rate of apoptosis activation (p b 0.05). More..
Effect of extracorporeal shock wave on proliferation and differentiation of equine adipose tissue-derived mesenchymal stem cells in vitro - Mesenchymal stem cells are regarded as common cellular precursors of the musculoskeletal tissue and are responsible for tissue regeneration in the course of musculoskeletal disorders. In equine veterinary medicine extracorporeal shock wave therapy (ESWT) is used to optimize healing processes of bone, tendon and cartilage. Nevertheless, little is known about the effects of the shock waves on cells and tissues. More..
Benefit of combined extracorporeal shock wave and bone marrow-derived endothelial progenitor cells in protection against critical limb ischemia in rats - We hypothesized that combined treatment with extracorporeal shock wave and bone marrow-derived endothelial progenitor cells might exert enhanced protection against critical limb ischemia in rats. More..
Shock wave-pretreated bone marrow cells further improve left ventricular function after myocardial infarction in rabbits - We tested whether shock wave (SW) offers additional benefits in improving left ventricular (LV) function after acute myocardial infarction (AMI) in rabbits receiving SW-treated autologous bone marrow-derived mononuclear cells (BMDMNCs) transplantation. More..
Mesenchymal stem cell-dependent formation of heterotopic tendon-bone insertions (osteotendinous junctions) - Ligament-to-bone and tendon-to-bone interfaces (entheses, osteotendinous junctions [OTJs]) serve to dissipate stress between soft tissue and bone. Surgical reconstruction of these interfaces is an issue of considerable importance as they are prone to injury and the integration of bone and tendon/ligament is in general not satisfactory. More..
"In vitro" and multicolor phenotypic characterization of cell subpopulations identified in fresh human adipose tissue stromal vascular fraction and in the derived mesenchymal stem cells - The stromal vascular fraction (SVF) is a heterogeneous cell population derived from the adipose tissue. There is still a lack of information concerning the characterization of the cell subpopulations constituting the SVF as well as its mesenchymal and haematopoietic potential. Furthermore there are great variations in its phenotypical characterization. More..
Shock waves activate in vitro cultured progenitors and precursors of cardiac cell lineages from the human heart - Postischemic cardiomyopathy remains one of the disorders in urgent need of effective noninvasive therapy. It is currently accepted that the isolation, expansion and application of resident cardiac stem cells may hold therapeutic promise for the future. Recently, it has been demonstrated that shock waves (SW) could enhance the expression of vascular endothelial growth factor (VEGF) and its receptor, Flt-1. More..
Low-energy shock wave for enhancing recruitment of endothelial progenitor cells: a new modality to increase efficacy of cell therapy in chronic hind limb ischemia - Stem and progenitor cell therapy is a novel approach to improve neovascularization and function of ischemic tissue. Enhanced tissue expression of chemoattractant factors such as stromal cell–derived factor 1 and vascular endothelial growth factor is crucial for the recruitment of circulating endothelial progenitor cells (EPCs) during acute ischemia. In chronic ischemia, however, expression of these chemoattractants is less pronounced, which results in insufficient EPC recruitment into the target tissue. Therefore, we investigated the effect of targeted extracorporeal shock wave (SW) application in order to facilitate EPC recruitment into nonischemic and chronic ischemic tissue. More..
Extracorporeal shock wave promotes growth and differentiation of bone-marrow stromal cells towards osteoprogenitors associated with induction of TGF-β1 - Extracorporeal shock-wave (ESW) treatment has been shown to be effective in promoting the healing of fractures. We aimed to determine whether ESW could enhance the growth of bone-marrow osteoprogenitor cells. We applied ESW to the left femur of rats 10 mm above the knee at 0.16 mJ/mm2 in a range of between 250 and 2000 impulses. Bone-marrow cells were harvested after ESW for one day and subjected to assessment of colony-forming unit (CFU) granulocytes, monocytes, erythocytes, megakaryocytes (CFU-Mix), CFU-stromal cells (CFU-S) and CFU-osteoprogenitors (CFU-O). More..
