Objective Mesenchymal stem cells (MSC) isolated from the Wharton jelly of the umbilical cord (UC-MSC) show great potential for the use in allogeneic stem cell therapies for various human diseases. However, the major limitation for the clinical use of allogeneic UC-MSC is their procoagulation activity, which is a consequence of expression of the tissue factor (TF), that can cause thromboembolism after transplantation, thus limiting their clinical usefulness. Preparation of UC-MSC without the TF (UCMSC-TF-) would enable safe clinical use of UC-MSC and bring their full therapeutic potential for treatment of patients. For this reason, preparation of UCMSC-TF- is the central goal of the “APApore4RNA” project. In the project, UCMSC-TF- will be prepared by utilizing the small interfering RNA (siRNA) directed against TF to silence the expression of TF. The project will develop a novel nanotechnology for ex vivo intracellular delivery of siRNA that will combine the use of biodegradable calcium hydroxyapatite (APA) nanoparticles (NPs) (fellow’s experience) and electroporation (EP) (experience of the company EDUCELL) to enable efficient, safe and reproducible transfection of UC-MSC. The use of APA NPs will be based on the fellow’s recent study published in Biomaterials that revealed their unique membrane-disruptive property that enables rapid permeation of payloads across plasma membrane. Moreover, as APA has low dielectric constant, it is expected that APA NPs will strongly improve the EP process by reducing the applied electric field required for reversible membrane permeabilization and consequently improve the safety and efficacy of EP. In addition, important goal of the “APApore4RNA” project is to gain fundamental knowledge about underlying mechanisms of APA-mediated electropermeabilization of plasma membrane and payload permeation across the membrane. Fields of science natural scienceschemical sciencesinorganic chemistryalkaline earth metalsmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicinetransplantationengineering and technologyindustrial biotechnologybiomaterialsnatural scienceschemical scienceselectrochemistrybioelectrochemistryelectroporation Keywords Calcium phosphates Mesenchymal stem cells RNAi siRNA Therapy Intracellular Delivery Nanoparticles Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator EDUCELL PODJETJE ZA CELICNO BIOLOGI JO DOO Net EU contribution € 162 040,32 Address PREVALE 9 1236 Trzin Slovenia See on map SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed. Yes Region Slovenija Zahodna Slovenija Osrednjeslovenska Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 162 040,32
