Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through RNA interference

Publication date: June 2018Source: Genes &Diseases, Volume 5, Issue 2Author(s): Shujuan Yan, Ruyi Zhang, Ke Wu, Jing Cui, Shifeng Huang, Xiaojuan Ji, Liping An, Chengfu Yuan, Cheng Gong, Linghuan Zhang, Wei Liu, Yixiao Feng, Bo Zhang, Zhengyu Dai, Yi Shen, Xi Wang, Wenping Luo, Bo Liu, Rex C. Haydon, Michael J. LeeAbstractMesenchymal stem cells (MSCs) are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic, chondrogenic and adipogenic lineages. We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood. Here, we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs. Using two different siRNA bioinformatic prediction programs, we design five siRNAs targeting mouse BMP9 (or simB9), which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors. We demonstrate that two of the five siRNAs, simB9-4 and simB9-7, exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs. Furthermore, simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers, matrix mineralization and ectopic bone formation from MSCs. Thus, our findings demonstrate the important ro...
Source: Genes and Diseases - Category: Genetics & Stem Cells Source Type: research

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Mesenchymal stromal cells from rat adipose tissue were transduced with adeno-associated viral (AAV) vector encoding stem cell factor SCF that stimulates proliferation of cardiac c-kit+ cells and improved cardiac function and survival of animals after myocardial infarction. Extracellular vesicles isolated from the medium conditioned by mesenchymal stromal cells by ultracentrifugation were characterized by Western blotting, transmission electron microscopy, nanoparticle tracking analysis, immunostaining, and mass spectrometry analysis. Using proteomic analysis, we identified transgenic SCF in extracellular vesicles released ...
Source: Bulletin of Experimental Biology and Medicine - Category: Biology Source Type: research
We present data over 4  years on the challenges and efficacy of unmanipulated T cell replete haplo SCTs with post-transplant cyclophosphamide (PTCy) in children diagnosed to have PIDs. We performed a retrospective study in the pediatric blood and marrow transplantation unit where all children less than 18 years of age d iagnosed to have PIDs and who underwent haplo SCT with PTCy from January 2014 to February 2018 were included in the study. Of the 16 transplants included in the study, 5 children were diagnosed to have Wiskott-Aldrich syndrome, 3 with congenital hemophagocytic lymphohistiocytosis, 2 each with Gris...
Source: Journal of Clinical Immunology - Category: Allergy & Immunology Source Type: research
Children and young adults who develop treatment-refractory infection with EBV, CMV, and/or adenovirus (AdV) after allogeneic hematopoietic stem cell transplant (allo-HSCT) have a dismal prognosis ( ≥90% mortality). Adoptive transfer of ex-vivo expanded virus-specific cytotoxic T lymphocytes (CTLs) is a treatment option for these patients, but the cell manufacturing process is labor-intensive and typically takes several weeks of culturing to complete. More recently, a culture-free method has been developed to directly isolate virus-specific T cells from peripheral blood for adoptive transfer.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 545 Source Type: research
Respiratory viral infections due to community-acquired respiratory viruses (CARVs) including respiratory syncytial virus (RSV), influenza, parainfluenza virus (PIV) and human metapneumovirus (hMPV) are detected in up to 40% of allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, in whom they may cause severe disease such as bronchiolitis and pneumonia that can be fatal. Given the lack of approved antiviral agents for these CARVs and our data demonstrating that adoptively transferred ex vivo-expanded virus-specific T cells (VSTs) can be clinically beneficial for the treatment of both latent [Epstein-Barr vi...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 544 Source Type: research
Yoon Pathologies induced by viral infections have undergone extensive study, with traditional model systems such as two-dimensional (2D) cell cultures and in vivo mouse models contributing greatly to our understanding of host-virus interactions. However, the technical limitations inherent in these systems have constrained efforts to more fully understand such interactions, leading to a search for alternative in vitro systems that accurately recreate in vivo physiology in order to advance the study of viral pathogenesis. Over the last decade, there have been significant technological advances that have allowed research...
Source: Viruses - Category: Virology Authors: Tags: Review Source Type: research
Safety and efficacy evaluations of an adeno-associated virus variant for preparing IL10-secreting human neural stem cell-based therapeutics, Published online: 28 January 2019; doi:10.1038/s41434-019-0057-8Safety and efficacy evaluations of an adeno-associated virus variant for preparing IL10-secreting human neural stem cell-based therapeutics
Source: Gene Therapy - Category: Genetics & Stem Cells Authors: Source Type: research
Abstract Genetic diseases affecting proteins and cells composing the blood may be treated by gene therapy using gene addition or gene editing methods. Protein deficiencies (e.g. hemophilia) are being approached using in vivo gene delivery by adeno-associated virus (AAV) vectors for therapeutic gene addition or gene editing. Blood cell diseases (e.g. sickle cell disease) are being approached using ex vivo gene addition or gene editing to treat isolated blood-forming hematopoietic stem cells or T cells that are then re-transplanted. In recent years, there has been much progress, and gene therapy is now routinely pro...
Source: Current Opinion in Biotechnology - Category: Biotechnology Authors: Tags: Curr Opin Biotechnol Source Type: research
Publication date: Available online 21 December 2018Source: The Journal of Allergy and Clinical Immunology: In PracticeAuthor(s): Katherine M. Harris, Blachy J. Davila, Catherine M. Bollard, Michael D. KellerViral infections are common and can be potentially fatal in patients with primary immunodeficiency disorders (PIDDs). Because viral susceptibility stems from poor to absent T-cell function in most patients with moderate to severe forms of PIDD, adoptive immunotherapy with virus-specific T cells (VSTs) has been used to combat viral infections in the setting of hematopoietic stem cell transplantation in multiple clinical ...
Source: The Journal of Allergy and Clinical Immunology: In Practice - Category: Allergy & Immunology Source Type: research
Adenovirus (AdV) is an increasingly recognized threat to the outcome of allogeneic hematopoietic stem cell transplants (allo-HCTs). Infection or reactivation is common after transplant because of the immunosuppressive therapies required for transplant success [1-4]. In most cases, emergent AdV infection is first identified within 100 days following transplant [1-4]. Several small-scale studies have shown that systemic AdV infection increases the risk of death, particularly in cases in which infection is prolonged and unresolved [5-16].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Adenovirus (AdV) is an increasingly recognized threat to successful outcomes after allogeneic hematopoietic stem cell transplantation (allo-HCT). Infection or reactivation is common after allo-HSCT, because of the immunosuppressive therapies required for successful transplantation [1 –4]. In most cases, emergent AdV infection is first identified within 100 days after transplantation [1–4]. Several small-scale studies have shown that systemic AdV infection increases the risk of death, particularly in cases of prolonged and unresolved infection [5–16].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
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