Benedetto Sacchetti, Alessandro Fatica, Melissa Sorci, Antonio Sorrentino, Michele Signore, Annamaria Cerio, Federica Felicetti, Alessandra De Feo, Elvira Pelosi, Alessandra Caré, Edoardo Pescarmona, Jan Oxholm Gordeladze, Mauro Valtieri
{"title":"Effect of miR-204&211 and RUNX2 control on the fate of human mesenchymal stromal cells.","authors":"Benedetto Sacchetti, Alessandro Fatica, Melissa Sorci, Antonio Sorrentino, Michele Signore, Annamaria Cerio, Federica Felicetti, Alessandra De Feo, Elvira Pelosi, Alessandra Caré, Edoardo Pescarmona, Jan Oxholm Gordeladze, Mauro Valtieri","doi":"10.1051/rmr/170004","DOIUrl":"https://doi.org/10.1051/rmr/170004","url":null,"abstract":"<p><p>MiR-204 and 211 enforced expression in murine mesenchymal stromal cells (MSCs) has been shown to induce adipogenesis and impair osteogenesis, through RUNX2 down-modulation. This mechanism has been suggested to play a role in osteoporosis associated with obesity. However, two further fundamental MSC functions, chondrogenesis and hematopoietic supporting activity, have not yet been explored. To this end, we transduced, by a lenti-viral vector, miR-204 and 211 in a model primary human MSC line, opportunely chosen among our MSC collection for displaying all properties of canonical bone marrow MSCs, except adipogenesis. Enforced expression of miR-204&211 in these cells, rescued adipogenesis, and inhibited osteogenesis, as previously reported in murine MSCs, but, surprisingly, also damaged cartilage formation and hematopoietic supporting activity, which were never explored before. RUNX2 has been previously indicated as the target of miR-204&211, whose down modulation is responsible for the switch from osteogenesis to adipogenesis. However, the additional disruption of chondrogenesis and hematopoietic supporting activity, which we report here, might depend on diverse miR-204&211 targets. To investigate this hypothesis, permanent RUNX2 knock-down was performed. Sh-RUNX2 fully reproduced the phenotypes induced by miR-204&211, confirming that RUNX2 down modulation is the major event leading to the reported functional modification on our MSCs. It seems thus apparent that RUNX2, a recognized master gene for osteogenesis, might rule all four MSC commitment and differentiation processes. Hence, the formerly reported role of miR204&211 and RUNX2 in osteoporosis and obesity, coupled with our novel observation showing inhibition of cartilage differentiation and hematopoietic support, strikingly resemble the clinical traits of metabolic syndrome, where osteoarthritis, osteoporosis, anaemia and obesity occur together. Our observations, corroborating and extending previous observations, suggest that miR-204&211-RUNX2 axis in human MSCs is possibly involved in the pathogenesis of this rapidly growing disease in industrialized countries, for possible therapeutic intervention to regenerate former homeostasis.</p>","PeriodicalId":42378,"journal":{"name":"Regenerative Medicine Research","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1051/rmr/170004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35221719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regenerative Medicine Research: striving to better serve the emerging field.","authors":"Y James Kang","doi":"10.1051/rmr/160001-s","DOIUrl":"https://doi.org/10.1051/rmr/160001-s","url":null,"abstract":"Regenerative Medicine Research, previously published by BioMed Central, is now transferred to its new publisher, EDP Sciences. As the Editor-in-Chief, I am excited to announce the continuation of this new open access, online journal. It remains to publish research relating to both the fundamental and practical aspects of regenerative medicine, with a particular emphasis on translational studies.","PeriodicalId":42378,"journal":{"name":"Regenerative Medicine Research","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1051/rmr/160001-s","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34668021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. J. Andersen, A. Knudsen, O. Wiborg, F. Mortensen
{"title":"Chronic stress does not impair liver regeneration in rats","authors":"K. J. Andersen, A. Knudsen, O. Wiborg, F. Mortensen","doi":"10.1186/s40340-015-0011-8","DOIUrl":"https://doi.org/10.1186/s40340-015-0011-8","url":null,"abstract":"","PeriodicalId":42378,"journal":{"name":"Regenerative Medicine Research","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2015-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40340-015-0011-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65860515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Moa Fransson, Johan Brännström, Ida Duprez, Magnus Essand, Katarina Le Blanc, Olle Korsgren, Peetra U Magnusson
{"title":"Mesenchymal stromal cells support endothelial cell interactions in an intramuscular islet transplantation model.","authors":"Moa Fransson, Johan Brännström, Ida Duprez, Magnus Essand, Katarina Le Blanc, Olle Korsgren, Peetra U Magnusson","doi":"10.1186/s40340-015-0010-9","DOIUrl":"https://doi.org/10.1186/s40340-015-0010-9","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stromal cells (MSC) have been under investigation for a number of therapies and have lately been in focus as immunosuppressive actors in the field of transplantation. Herein we have extended our previously published in vitro model of MSC-islets in an experimental setting of islet transplantation to the abdominal muscle. Human islets coated with luciferase-GFP transduced human MSC were transplanted to the abdomen muscle tissue of NOD-scid ILR2γ(null) mice and cellular interactions were investigated by confocal microscopy.</p><p><strong>Results: </strong>The MSC reduced fibrotic encapsulation and facilitated endothelial cell interactions. In particular, we show a decreased fraction of αSMA expressing fibrotic tissue surrounding the graft in presence of MSC-islets compared to islets solely distributed into the muscle tissue. Also, in the presence of MSC, human islet endothelial cells migrated from the center of the graft out into the surrounding tissue forming chimeric blood vessels with recipient endothelial cells. Further, in the graft periphery, MSC were seen interacting with infiltrating macrophages.</p><p><strong>Conclusions: </strong>Here, in our experimental in vivo model of composite human islets and luciferase-GFP-transduced human MSC, we enable the visualization of close interactions between the MSC and the surrounding tissue. In this model of transplantation the MSC contribute to reduced fibrosis and increased islet endothelial cell migration. Furthermore, the MSC interact with the recipient vasculature and infiltrating macrophages.</p>","PeriodicalId":42378,"journal":{"name":"Regenerative Medicine Research","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2015-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40340-015-0010-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34056065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carlos Alberto Palmeira Sarmento, Marcio Nogueira Rodrigues, Renato Zonzini Bocabello, Andrea Maria Mess, Maria Angelica Miglino
{"title":"Pilot study: bone marrow stem cells as a treatment for dogs with chronic spinal cord injury.","authors":"Carlos Alberto Palmeira Sarmento, Marcio Nogueira Rodrigues, Renato Zonzini Bocabello, Andrea Maria Mess, Maria Angelica Miglino","doi":"10.1186/2050-490X-2-9","DOIUrl":"https://doi.org/10.1186/2050-490X-2-9","url":null,"abstract":"<p><strong>Background: </strong>Chronic Spinal Cord injury is a common, severe, and medically untreatable disease. Since the functional outcomes of acute and experimental chronic spinal cord injury have been shown to improve with stem cell therapy, a case study was conducted to test if the application of stem cell also regenerates chronic SCI dysfunction. Transplantation of foetal bone marrow stem cells was applied in seven dogs with chronic spinal cord injury. Magnetic resonance images and assessments of symptoms according to the Olby scale were used to diagnose the severity of injury.</p><p><strong>Result: </strong>All dogs improved locomotor and sensory function when examined 90 days after surgery, and showed increased movement of the hind limbs, and were able to stand upright, as well as to take small steps. Tail tone was observed in seven dogs, pain reflexes and defecation return were observed in five dogs.</p><p><strong>Conclusion: </strong>The transplantation of bone marrow stem may be a promising, reliable and safe treatment for chronic spinal cord injury.</p>","PeriodicalId":42378,"journal":{"name":"Regenerative Medicine Research","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2014-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2050-490X-2-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33312937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Promising targets of cell death signaling of NR2B receptor subunit in stroke pathogenesis.","authors":"Shu Shu, Lei Pei, Youming Lu","doi":"10.1186/2050-490X-2-8","DOIUrl":"https://doi.org/10.1186/2050-490X-2-8","url":null,"abstract":"<p><p>Stroke is an acute cerebrovascular disease caused by acute brain artery bursting or cerebral embolism that leads to neuronal death and severe dysfunction of synaptic transmission. Neuronal damage after stroke remains a major cause of morbidity and mortality worldwide and affects 795 000 of lives every year in United States. However, effective treatments remain lacking, which makes the identification of new therapeutic targets a matter of great importance. N-methyl-D-aspartate glutamate (NMDA) receptor is important both in the normal synaptic transmission and in the neuronal death after stroke. Accumulated evidences show NMDA receptor downstream effectors, such as PSD-95, DAPK1, and ERK, had been revealed to be linked with neuronal damage. Based on our recent studies, we review the promising targets of the NMDA receptor downstream signaling involved in stroke treatment. This review will provide the concept of NR2B downstream signaling in neuronal death after stroke and provide evidences for developing better NMDAR-based therapeutics by targeting downstream proteins. </p>","PeriodicalId":42378,"journal":{"name":"Regenerative Medicine Research","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2014-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2050-490X-2-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33312936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell-based therapy in lung regenerative medicine.","authors":"Jibing Yang, Zhenquan Jia","doi":"10.1186/2050-490X-2-7","DOIUrl":"https://doi.org/10.1186/2050-490X-2-7","url":null,"abstract":"<p><p>Chronic lung diseases are becoming a leading cause of death worldwide. There are few effective treatments for those patients and less choices to prevent the exacerbation or even reverse the progress of the diseases. Over the past decade, cell-based therapies using stem cells to regenerate lung tissue have experienced a rapid growth in a variety of animal models for distinct lung diseases. This novel approach offers great promise for the treatment of several devastating and incurable lung diseases, including emphysema, idiopathic pulmonary fibrosis, pulmonary hypertension, and the acute respiratory distress syndrome. In this review, we provide a concise summary of the current knowledge on the attributes of endogenous lung epithelial stem/progenitor cells (EpiSPCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) in both animal models and translational studies. We also describe the promise and challenges of tissue bioengineering in lung regenerative medicine. The therapeutic potential of MSCs is further discussed in IPF and chronic obstructive pulmonary diseases (COPD). </p>","PeriodicalId":42378,"journal":{"name":"Regenerative Medicine Research","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2014-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2050-490X-2-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33312935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Heart regeneration, stem cells, and cytokines.","authors":"Na Li, Chuan Wang, LiXin Jia, Jie Du","doi":"10.1186/2050-490X-2-6","DOIUrl":"https://doi.org/10.1186/2050-490X-2-6","url":null,"abstract":"<p><p>The human heart has limited regenerative capacity, which makes the reparative response after the cardiac infarction quite challenging. During the last decade, stem cells have become promising candidates for heart repair, owing to their potent differentiation capacity and paracrine cytokine secretion. Among the different types of stem cells, mesenchymal stem cells have high proliferative potential and secrete numerous cytokines, growth factors, and microRNAs. The paracrine cytokines play important roles in cardiac regeneration, neovascularization, anti-apoptosis, and anti-remodeling mechanisms, among others. This review summarizes the cytokines secreted by stem cells and their relative signaling pathways, which represent key mechanisms for heart regeneration and may serve as a promising future therapeutic strategy for myocardial infarction patients. </p>","PeriodicalId":42378,"journal":{"name":"Regenerative Medicine Research","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2014-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2050-490X-2-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33313051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Isolation and characterization of endothelial progenitor cells from Rhesus monkeys.","authors":"Wen Sun, Lily Zheng, Pengfei Han, Y James Kang","doi":"10.1186/2050-490X-2-5","DOIUrl":"https://doi.org/10.1186/2050-490X-2-5","url":null,"abstract":"<p><strong>Background: </strong>Endothelial progenitor cells (EPCs) are increasingly becoming a major focus of regenerative medicine research and practice. The present study was undertaken to establish an appropriate procedure for isolation and characterization of EPCs from Rhesus monkeys for regenerative medicine research.</p><p><strong>Result: </strong>Selective CD34+ and nonselective mononuclear EPCs were isolated from bone marrow and cultured under varying conditions. The results showed that nonselective mononuclear EPCs were a better choice for high yield of the target cells. The cells grew in M 200 better than in EGM-2, and supplementation with fetal bovine serum promoted cell proliferation; but serum level at 7.5% was better than at 10%. In addition, surface coating of the culture dishes with human fibronectin significantly improved the proliferation and ontogeny of the isolated EPCs. Immunocytochemistry including detection of markers CD34, CD133 and CD31 and double-staining for Ac-LDL and lectin verified the purity of the cultured mononuclear EPCs.</p><p><strong>Conclusion: </strong>By a thorough analysis, we established a practical procedure for isolation and propagation of EPCs from Rhesus monkeys. This procedure would help using these valuable cells for regenerative medicine research.</p>","PeriodicalId":42378,"journal":{"name":"Regenerative Medicine Research","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2014-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2050-490X-2-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33313050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Human induced pluripotent stem cell for modeling cardiovascular diseases.","authors":"Ping Liang, Jie Du","doi":"10.1186/2050-490X-2-4","DOIUrl":"https://doi.org/10.1186/2050-490X-2-4","url":null,"abstract":"<p><p>The invention of the induced pluripotent stem cell (iPSC) technology allows patient-specific, mature somatic cells to be converted into an unlimited supply of pluripotent stem cells (PSCs). These iPSCs can then in turn be differentiated into any cell type including neurons, cardiac cells, pancreatic cells, liver cells, blood cells or enterocytes. Although cardiovascular disease (CVD) is a leading cause of death in the world, the limited cell derivation and cell number in cardiac tissue makes it difficult to study the CVDs using the existing cardiac cell model. By differentiating the patient-specific iPSCs into cardiomyocytes, scientists can generate iPSC-based 'disease in a dish' models and use them to better understand disease mechanism. Here we review the current progress in using iPSC-derived cardiomyocytes to model human CVDs. </p>","PeriodicalId":42378,"journal":{"name":"Regenerative Medicine Research","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2014-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2050-490X-2-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33313048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}