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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Publication date: Available online 4 October 2018Source: Life SciencesAuthor(s): Jingjing Liu, Yuxuan Xu, Qiaofang Wu, Qi Ding, Weixin FanAbstractObjectiveStem cell transplantation is a promising tool to treat burn injuries. However, the inflammatory microenvironment in damaged skin limits the efficiency of stem cell-based therapy via poorly understood mechanisms. The aim of our study is to explore the contribution and mechanism of Sirtuin-1 (Sirt1) in TNFα-mediated inflammatory stress in hair follicle stem cells (HFSCs).MethodsCellular viability was determined using the MTT assay, TUNEL staining, western blot analys...
Source: Life Sciences - Category: Biology Source Type: research
In this study we use our virotherapy Celyvir with syngeneic and allogeneic mouse mesenchymal stem cells to determine their antitumor efficacy in a C57BL/6 murine adenocarcinoma model. Adoptive transfer of splenocytes from treated mice to new tumor-bearing mice followed by a secondary adoptive transfer to a third group was performed. Similar reduction of tumor growth and systemic activation of the innate and adaptive immune system was observed in groups treated with syngeneic or allogeneic mesenchymal stem cells loaded with ICOVIR-5. Moreover, a different pattern of infiltration was observed by immunofluorescence in Celyvir...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
In this study, we genetically engineered MSCs using ex vivo adeno-associated virus (AAV) transduction to overexpress Akt1 and Wnt11, which are well-characterized genes involved in MSC proliferation and cardiac differentiation. Our results showed that infection with AAV-Akt1-Wnt11 significantly upregulated the growth and proliferation of MSCs, as compared with those infected with AAV-Akt1 or AAV-Wnt11. In addition, co-expression of Akt1 and Wnt11 markedly promoted the expression of cardiac markers including NK2 transcription factor related 5, GATA-binding protein 4, α-myosin MHC and brain natriuretic protein. Notably,...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Abstract Parkinson's disease (PD) is a frustrating condition characterized by motor and nonmotor deficits majorly caused by the loss of dopaminergic cells in the substantia nigra pars compacta (SNc) and destruction of the nigrostriatal pathway. Despite the very respectable advances in cutting-edge approaches for the treatment of PD, there exist numerous challenges that have incapacitated the definitive treatment of this disease. This review emphasized the development of various non-pharmaceutical therapeutic approaches and mainly highlighted the cutting-edge treatments for PD including gene- and stem cell-based th...
Source: Current Gene Therapy - Category: Genetics & Stem Cells Authors: Tags: Curr Gene Ther Source Type: research
Publication date: September 2018Source: The Lancet Haematology, Volume 5, Issue 9Author(s): Ryan Malcolm Hum, David Deambrosis, Su Han Lum, Emma Davies, Denise Bonney, Malcolm Guiver, Andrew Turner, Robert Francis Wynn, Prashant HiwarkarSummaryBackgroundFaecal shedding of adenovirus following allogeneic haematopoietic stem-cell transplantation (HSCT) is an early sign of loss of immune control over adenovirus, but there is no consensus on the role of monitoring of faecal adenoviral load by serial testing. We investigated whether serial faecal PCR monitoring could predict the risk of adenoviraemia and survival outcomes after...
Source: The Lancet Haematology - Category: Hematology Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, researchers reprogrammed Müller glia cells into rod photoreceptors in the retinas of uninjured mice, both in wildtype mice and in two strains that serve as models of congenital blindness. The team developed a two-step technique, first injecting an adeno-associated virus with a gene that expresses β-catenin, a protein that helps the glia re-enter the cell cycle, into the retinas of the four-week-old mice. Two weeks later, the mice received a second injection of an adeno-associated virus with the genes that express the transcription factors Otx2, Crx, and Nrl - shown in past studies to aid in the dev...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
In recent years, researchers working on forms of telomerase gene therapy have produced evidence to show that increased levels and activity of telomerase does not raise cancer risk in mice. The open access paper and publicity materials noted below report the latest example. Extra telomerase increases the sort of activities that are beneficial in the context of improved regenerative capacity, but might be thought to raise the risk of cancer when they take place in the damaged environment of old tissue. This means more stem cell activity, more cellular replication, and so forth. Somatic cells are limited in the degree ...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Authors: Zhang F, Guo F Abstract In the present study, we aimed to investigate the effect of transplantation of cardiac stem cells (CSCs) overexpressing integrin-linked kinase (ILK) on cardiac function of rats with acute myocardial infarction (MI). A total of 60 rats were randomly divided into normal saline (NS) group (n=20), green fluorescent protein (GFP)-CSC group (n=20) and ILK-CSC group (n=20). In the ILK-CSC group, CSCs in rats were transfected with GFP adenovirus vector overexpressing ILK. The rat model of MI was established. The cardiac function 4 weeks after transplantation was detected via echocardiograph...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Authors: Yan X, Zhou Z, Guo L, Zeng Z, Guo Z, Shao Q, Xu W Abstract Bone fractures are a worldwide public health concern. Previous studies have demonstrated that bone morphogenetic protein-7 (BMP7) gene transfer or mesenchymal stem cells (MSCs) transplantation may be a promising novel therapeutic approach. Therefore, the aim of the present study was to observe the effect of bone BMP7 transfer to MSCs on fracture healing. Bone marrow-derived MSCs (BMSCs) from New Zealand white rabbits were isolated and identified using flow cytometry. A recombinant BMP7 overexpressing adenovirus vector (Adv) was constructed and tran...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
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