Susceptibility of Human Placenta Derived Mesenchymal Stromal/Stem Cells to Human Herpesviruses Infection (original) (raw)
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PLoS ONE, 2012
Background: Mesenchymal stem cells (MSC) are promising candidates for cell therapy, as they migrate to areas of injury, differentiate into a broad range of specialized cells, and have immunomodulatory properties. However, MSC are not invisible to the recipient's immune system, and upon in vivo administration, allogeneic MSC are able to trigger immune responses, resulting in rejection of the transplanted cells, precluding their full therapeutic potential. Human cytomegalovirus (HCMV) has developed several strategies to evade cytotoxic T lymphocyte (CTL) and Natural Killer (NK) cell recognition. Our goal is to exploit HCMV immunological evasion strategies to reduce MSC immunogenicity.
Biology of Blood and Marrow Transplantation, 2010
To safely reach the coast, waves have to be passed. Waves can range in size from small ripples to huge rogue waves, influenced by the wind, coast surface and the tide. Patients after stem cell transplantation have to survive waves of viral reactivations, alloreactive disease and infections. As the danger of the waves changes continuously, the occurrence of complications is different in every individual. Although important progress has been made, the complex associations between viral reactivations and allo-reactive disease are still an important treatment-dilemma. We aim to control complications by reducing the waves and putting up wave breakers. Developing strategies to overcome the critical first months after stem cell transplantation without complications will eventually lead towards a safer stem cell transplantation procedure and will cure more patients.
Human Reproduction, 2008
BACKGROUND: Intrauterine stem cell transplantation is a promising approach for early onset genetic diseases. However, its utility is limited by the development of the fetal immune system after 14 weeks gestation. An ex vivo gene therapy approach targeting autologous first trimester stem cells to replace the missing or defective gene product should overcome this barrier. We investigated the feasibility of harvesting circulating first trimester human fetal mesenchymal stem cells (hfMSCs) for ex vivo gene therapy. METHODS: Thin-gauge embryofetoscopic-directed or ultrasound-guided blood sampling (FBS) was performed in 18 pre-termination fetuses at a mean of 10 10 (range 7 12 to 13 14 ) weeks gestation through extra-fetal vessels. Harvested blood was plated for isolation of hfMSC and transduced by lentiviruses. RESULTS: FBS was successful in 12/18 procedures (67%). Success rates were comparable in fetoscopic (4/6) and ultrasound-guided (8/12) procedures, but procedural time was shorter in the ultrasound-guided arm (P 5 0.01). Fetal bradycardia occurred post-FBS in 33% and 25% of fetoscopic and ultrasound cases, respectively, 5 min post-procedure. hfMSCs were isolated in two-thirds of cases, with high efficiency lentiviral transduction achieved without affecting short-term cell renewal. CONCLUSIONS: This phase-one study demonstrates the feasibility of the ex vivo fetal gene therapy approach, in which harvested hfMSCs are genetically manipulated prior to infusion back into the fetus where they should engraft and home to injured tissues. The fetal ex vivo gene therapy paradigm is also of relevance to haemopoietic stem cells to treat inherited haematological diseases. Optimization of stem cell harvest and longer-term safety is required before translation into clinical trials in ongoing pregnancies.
Background and Aims: Mesenchymal stem cells (MSCs) are attractive targets for cell and gene therapy, because they can differentiate into many cell lineages. Hence, finding an efficient and suitable method for transferring of genetic materials to these cells is very essential. In this study, we evaluated the efficiency of two methods of gene transferring, viral and nonviral, in transfection of mouse MSCs, comparatively. Materials and methods: MSCs were isolated from mouse bone marrow and their ability to differentiate into osteocyte and adipocyte lineages and their surface markers were evaluated. Then, the efficiency of two methods of nonviral gene transferring; calcium phosphate, and cationic lipid reagents (Lipofectamine™ LTX with Plus™ Reagent and Turbofect TM); and also lentivirus vector were examined in transfection of mouse MSCs with green fluorescent protein (GFP) plasmid. Results: The isolated MSCs successfully differentiated to osteocytes and adipocytes. They were positive for CD24, CD29 and CD44; and negative for CD11b and CD45 cell surface markers. Nonviral gene transferring methods were completely inefficient in transfection of mouse MSCs; whereas calcium phosphate precipitate was completely toxic to mouse MSCs and cationic lipids only transfected less than three percent of the cells. In contrast, high transfection rate and GFP expression (above 70%) was seen with lentivirus vector. Conclusions: it seems that mouse MSCs are refractory to nonviral gene transferring methods. In contrast, lentivirus-mediated gene transfer methods may be an efficient tool for transfection of mouse MSCs without any interference on their phenotype and differentiation potential.
Mesenchymal Stem Cell Transplantation for COVID-19
Athenaeum Scientific Publishers, 2020
In-vitro, Mesenchymal Stem Cell (MSC) populations with potentials of similar multi-lineage differentiation have been obtained from several Bone Marrow (BM) and non-bone marrow tissues, including umbilical cord, placenta, amniotic fluid, adipose tissue, and peripheral blood [1-10]. The clonogenic BM-human MSCs fraction ranges from 10 to 100 Colony-Forming Unit-Fibroblast (CFU-F) per 106 Marrow Mononuclear Cells (MNCs) [11]. BM-human MCSs are characterized by lacking CD11b, CD14, CD19, D34, CD45, CD79α, and Human Leukocyte Antigen (HLA)-DR expression; positive expression of surface antigens CD73, CD90, and CD105; multipotency (i.e., chondrogenic, osteogenic, and adipogenic); and their adherence to plastic [11]. By the year 2000, clinicians increasingly had become interested in intravenously applied MSC therapy [12]. A previous study demonstrated that both human and murine MCSs can induce immune suppression by attracting and killing auto reactive T cells via FasL, therefore stimulating Transforming Growth Factor-beta (TGF-β) production by macrophages and generation of regulatory T cells [13]. The dying T cells that is caused by the interaction involving the MSC-induced Monocyte Chemoattractant Protein-1 (MCP-1) secretion in turn activate macrophages to produce TGF-β, then stimulating regulatory T cells and promoting immune tolerance [14]. The capacity of MSCs for in-vivo differentiation and engraftment and by their efficacy in promoting wound healing highlighted its clinical relevance [15-21].
Journal of biomedicine & biotechnology, 2011
Hematopoietic stem cells recipients remain susceptible to opportunistic viral infections including herpes simplex virus type-1 (HSV-1). The purpose of this investigation was to analyze susceptibility of human mesenchymal stem cells (hMSCs) to HSV-1 infection and identify the major entry receptor. Productive virus infection in hMSCs was confirmed by replication and plaque formation assays using a syncytial HSV-1 KOS (804) virus. To examine the significance of entry receptors, RT-PCR and antibody-blocking assays were performed. RT-PCR data showed the expression of gD receptors: nectin-1, 3-O sulfotransferase-3 (3-OST-3), and HVEM. Antibody-blocking assay together with heparinase treatment suggested an important role for HS and 3-O-sulfated heparan sulfate (3-OS HS), but not nectin-1 or HVEM, in mediating HSV-1 entry and spread in hMSCs. Taken together, our results provide strong evidence demonstrating that HSV-1 is capable of infecting hMSCs and HS and 3-OS HS serve as its entry recep...