A5028384698- Hemophilia Treatment and Research
- Platelet Disorders and Treatments
- Liver physiology and pathology
- Blood Coagulation and Thrombosis Mechanisms
- Chronic Myeloid Leukemia Treatments
- Cancer-related gene regulation
- RNA Interference and Gene Delivery
- Pancreatic function and diabetes
- Tissue Engineering and Regenerative Medicine
- CAR-T cell therapy research
- Renal and related cancers
- Virus-based gene therapy research
- Mesenchymal stem cell research
- Adenosine and Purinergic Signaling
- Immune cells in cancer
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Immune Response and Inflammation
- CRISPR and Genetic Engineering
- Biomedical Ethics and Regulation
- Hippo pathway signaling and YAP/TAZ
- Viral Infectious Diseases and Gene Expression in Insects
- Electrospun Nanofibers in Biomedical Applications
- Biochemical and Molecular Research
- Phagocytosis and Immune Regulation
Università degli Studi del Piemonte Orientale “Amedeo Avogadro”
2015-2024
Department of Medical Sciences
2023-2024
KU Leuven
2023
University of Edinburgh
2013
MRC Centre for Regenerative Medicine
2013
National Institute of Pathology
2010
Abstract Permanent epigenetic silencing using programmable editors equipped with transcriptional repressors holds great promise for the treatment of human diseases 1–3 . However, to unlock its full therapeutic potential, an experimental confirmation durable after delivery transient in vivo is needed. To this end, here we targeted Pcsk9 , a gene expressed hepatocytes that involved cholesterol homeostasis. In vitro screening different editor designs indicated zinc-finger proteins were...
A large fraction of factor VIII in blood originates from liver sinusoidal endothelial cells although extrahepatic sources also contribute to plasma levels. Identification cell-types other than with the capacity synthesize and release will be helpful for therapeutic approaches hemophilia A. Recent cell therapy bone marrow transplantation studies indicated that Küpffer cells, monocytes mesenchymal stromal could sufficient amount ameliorate bleeding phenotype hemophilic mice. To further...
Hemophilia A (HA) is an X-linked bleeding disease caused by factor VIII (FVIII) deficiency. We previously demonstrated that FVIII produced specifically in liver sinusoid endothelial cells (LSECs) and to some degree myeloid cells, thus, the present work, we seek restrict expression of transgene these using cell-specific promoters. With this approach, aim limit immune response a mouse model lentiviral vector (LV)-mediated gene therapy encoding FVIII. To increase target specificity expression,...
We generated patient-specific disease-free induced pluripotent stem cells (iPSCs) from peripheral blood CD34+ and differentiated them into functional endothelial (ECs) secreting factor VIII (FVIII) for gene cell therapy approaches to cure hemophilia A (HA), an X-linked bleeding disorder caused by F8 mutations. iPSCs were transduced with a lentiviral vector carrying FVIII transgene driven endothelial-specific promoter (VEC) bona fide ECs using optimized protocol. FVIII-expressing...
Liver sinusoidal endothelial cells (LSECs) are specialized endocytic that clear the body from blood-borne pathogens and waste macromolecules through scavenger receptors (SRs). Among various SRs expressed by LSECs is stabilin-2 (STAB2), a class H SR binds to several ligands, among which endogenous coagulation products. Given well-established tolerogenic function of LSECs, we asked whether STAB2 promoter (STAB2p) would enable us achieve LSEC-specific lentiviral vector (LV)-mediated transgene...
Osteoclasts are resident cells of the bone that primarily involved in physiological and pathological remodeling this tissue. Mature osteoclasts multinucleated giant generated from fusion circulating precursors originating monocyte/macrophage lineage. During inflammatory conditions vivo, de novo osteoclastogenesis is observed but it currently unknown whether, besides increased osteoclast differentiation undifferentiated precursors, other cell types can generate a phenotype with resorbing...
Defects in genes encoding ribosomal proteins cause Diamond Blackfan Anemia (DBA), a red cell aplasia often associated with physical abnormalities. Other bone marrow failure syndromes have been attributed to defects components but the link between erythropoiesis and ribosome remains be fully defined. Several lines of evidence suggest that synthesis lead "ribosomal stress" p53 activation either cycle arrest or induction apoptosis. Pathways independent also proposed play role DBA pathogenesis....
A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted cells in heart. Better engraftment can be achieved if are administered as aggregates, which maintain their extra-cellular matrix (ECM). We have generated spheroid aggregates less than 24 h by seeding human cardiac progenitor (hCPCs) onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained expression stemness/mesenchymal ECM markers, growth factors...
Here we describe a successful gene therapy approach for hemophilia A (HA), using the natural F8 promoter (pF8) to direct replacement factor VIII (FVIII)-secreting cells. The sequence and regulatory elements involved in modulation of expression are still poorly characterized biased by historical assumption that FVIII is mainly hepatocytes. Bioinformatic analyses have highlighted an underestimated complexity at this locus, suggesting activation pF8 more cell types than those previously...
Liver sinusoidal endothelial cells (LSECs) form the predominant microvasculature in liver where they carry out many functions including secretion of coagulation factor VIII (FVIII). To investigate early origins this lineage, we develop an efficient and scalable protocol to produce human pluripotent stem cell (hPSC)-derived LSEC progenitors characterized as venous (VECs) from different mesoderm subpopulations. Using a sensitive quantitative vascular competitive transplantation assay,...
Hepatocyte growth factor (HGF), a pleiotropic cytokine with mitogenic, motogenic, morphogenic, and antiapoptotic effects in various cell types, is cardioprotective that can counteract the loss of cardiomyocytes usually observed cardiac diseases. HGF quite unstable molecule its biologically active heterodimeric form. Since all HGF-induced biological responses are mediated by high-affinity tyrosine kinase receptor (Met/HGF-R) encoded Met gene, we asked whether monoclonal antibody (MAb)...
The c-MET proto-oncogene, encoding the p190 hepatocyte growth factor tyrosine kinase receptor, can acquire oncogenic potential by multiple mechanisms, such as gene rearrangement, amplification and overexpression, point mutation, ectopic expression, all resulting in its constitutive activation. Hepatocyte receptor truncated forms are generated post-translational cleavage: p140 p130 lack domain inactive. Their C-terminal remnant fragments generally undetectable normal cells, but a...
The emerging field of tissue engineering and regenerative medicine is a multidisciplinary science that based on the combination reliable source stem cells, biomaterial scaffolds, cytokine growth factors. Adult mesenchymal cells are considered important for applications in this field, adipose has revealed to be an excellent them. Indeed, adipose-derived (ASCs) can easily isolated from stromal vascular fraction (SVF) tissue. During isolation propagation murine ASCs, we observed appearance...
Abstract Lentiviral vectors (LV) are efficient vehicles for in vivo gene delivery to the liver. LV integration into chromatin of target cells ensures their transmission upon proliferation, thus allowing potentially life-long therapy following a single administration, even young individuals. The glycoprotein vesicular stomatitis virus (VSV.G) is widely used pseudotype LV, as it confers broad tropism and high stability. baculovirus-derived GP64 envelope protein has been proposed an alternative...
Hemophilia A (HA) is a rare bleeding disorder caused by deficiency/dysfunction of the FVIII protein. As current therapies based on frequent infusions are not definitive cure, long-term expression in endothelial cells through lentiviral vector (LV)-mediated gene transfer holds promise one-time treatment. Thus, here we sought to determine whether LV-corrected blood outgrowth (BOECs) implanted prevascularized medical device (Cell Pouch) would rescue phenotype HA mice. To this end, BOECs from...
Hepatocyte growth factor (HGF) is involved in the pathogenesis of Kaposi’s sarcoma (KS), most frequent neoplasia patients with AIDS, characterized by proliferating spindle cells, infiltrating inflammatory angiogenesis, edema, and invasiveness. In vitro , this sustains biological behavior KS derived after activation its receptor downstream MAPK AKT signals. other cell types, namely endothelial epithelial movement, proliferation, survival stimulated HGF factors cytokines depend on...