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Development of mucoadhesive films with amniotic membrane homogenate for the potential application in oral tissue regeneration

Project leader: Dr Ivana Okić Đorđević

Project collaborators:

Dr Hristina Obradović, dr Drenka Trivanović, dr Ivana Drvenica, dr med Sanja Momčilović, number: 337-00-110/2023-05/36

Duration of the project: Jul 2023 – Jun 2025

Leading Institution:

Institute for medical Research, University of Belgrade

Collaborating Institution: Institute of cell biology, University of Ljubljana

Description of the project:

Human amniotic membrane (hAM) is an available, inexpensive, and biocompatible collagen-based extracellular matrix with the cells derived from human placenta. hAM and its derivatives possess anti-inflammatory and regenerative properties. Until now, hAM has been used for post-operative and post-traumatic skin defects, intra-oral and genital reconstruction, and ophthalmologic disorders.

In recent decades, the regenerative and modulatory properties of stem cells (SCs) have gained the attention of scientists indicating the possibility of their use in cell therapy. Periodontal ligament SCs (PDLSCs), obtained after tooth extraction for orthodontic reasons are recently discovered cells playing a crucial role in oral tissue homeostasis. Since the outcomes of currently available wound healing treatment approaches of oral tissues are expensive and sometimes not predictable, the search for new molecules with regenerative potential is an important goal in oral tissue regeneration. For this purpose, the objectives of this project include the influence of hAM on wound healing and regenerative potential of PDLSCs.

Тип пројекта:

International Projects

Establishing of Alpl gene-deficient patient cell line for investigation of metabolic background of hip osteoarthritis

Project leader: Dr Trivanović Drenka

Project collaborators:

Dr Slavko Mojsilović, dr Ivana Okić-Đorđević, dr Aleksandra Jauković, dr Tamara Kukolj, dr Hristina Obradović, Anđelija Petrović, Milena Živanović

Project number: Q422RSV70

Duration of the project: January 2023 – December 2023

Leading Institution:

Institut za medicinska istraživanja Univerziteta u Beogradu

Description of the project:

The role of tissue non-specific alkaline phosphatase (TNAP) in osteoarthritis (OA) has not been fully clarified. High expression of TNAP as ectonucleotidase is associated with ATP degradation and production of adenosine, which can again trigger and support inflammatory calcifying conditions, but also decrease mineralization of the subchondral bone in OA. Thus, we anticipate that TNAP beyond its well-known contribution to mineralization, participates in profiling of cellular metabolism. To verify the assumption that TNAP controls metabolism of cells from OA patients, we attempt to apply genome editing (GE) techniques to silence and knockout Alpl gene in OA patient-derived mesenchymal stromal cells. We will perform Alpl gene silencing (commercially available siRNA) and CRISPR/Cas9 technique to establish OA patient-derived GE cell lines (clones) with Alpl gene silencing/knockout for investigation of metabolic roles of TNAP in OA patients.

Тип пројекта:

International Projects

Metabolic effects of bone marrow adipose tissue on multiple myeloma

Project leader : Dr Trivanović Drenka

Project collaborators:

Dr Ivana Okić Djordjević, dr Aleksandra Jauković, dr Marijana Kovačić, Sanja Momčilović doktorand, Milena Živanović doktorand

Project number:

Duration of the project: 2023 – 2024

Leading Institution:

Julius-Maximilians-Universität Würzburg – Department for Musculoskeletal Tissue Regeneration
Institut za ortopediju ”Banjica”

Description of the project:

Multiple myeloma (MM) is the hematologic malignancy and incurable clonal disease of the plasma cell that grows within the bone marrow (BM) causing destructive bone lesions. As disease of elderly, MM is associated with increased bone marrow adipose tissue (BMAT) that might provide supportive microenvironment for MM cell growth, survival and drug resistance. Since adipocytes were shown to support cancer cell growth by influencing cell mitochondrial activity and lipid metabolism, this project aims to decipher whether BM adipocytes (BMAd) population represents one of the key regulators of MM persistence by controlling fatty acid oxidation (FAO) in MM cells. To address this issue, we will determine the lipid profile of femoral bone marrow, as well as metabolic fitness of plasma and BMAT cells in MM patients. In parallel, lipid and mitochondria exchange at single-cell level will be analyzed in advanced cultures of BMAT and MM cells. Particularly, the role of Kisspeptin-1 receptor signaling in BMAT and MM fatty acid exchange will be explored.

Тип пројекта:

International Projects

The interaction of p53 and Wnt-signaling in the stemness of mesenchymal stem cells

Project leader: Dr Jelena Krstić

Project collaborators:

Dr Trivanović Drenka, dr Obradović Hristina, dr Kukolj Tamara, dr Okić-Đorđević Ivana

Project number: 451-03-01039/2015-09/31

Duration of the project: 2016 – 2017

Leading Institution: N/A

Description of the project:

Self-renewal and differentiation of stem cells are finely controlled processes that contribute to the maintenance of tissue homeostasis. Transcription factor p53 has been known to regulate these processes in embryonic and adult stem cells in a dual way via the Wnt signaling pathway. Within this project, the role of p53 and Wnt signaling in the regulation of self-renewal and differentiation of mesenchymal stem cells of perinatal tissues (umbilical cord and amnion) was investigated by analyzing the expression of pluripotency markers (Nanog, Sox2, Oct4) and markers of adipogenic/osteogenic differentiation potential (PPARγ, adiponectin, Runx2, osteocalcin) under the conditions of induced or suppressed p53 expression. This was achieved by different gene transfection approaches, as well as the use of specific pharmacological activators/inhibitors (nutlin, pifithrin).

Тип пројекта:

International Projects

Human culture-expanded adipose stromal/stem cells: serial expansion and maintenance of their proliferative, multipotential and regulatory properties

Води : Dr Jauković Aleksandra

Сарадници на пројекту: Dr Bugarski Diana, dr Kocić Jelena, dr Trivanović Drenka

Број пројекта: 451-03-02338/2012-14/05

Трајање пројекта: 2013 – 2014

Водећа институција:

Опис пројекта:

The use of stem/stromal cells derived from adipose tissue as an autologous source of various differentiated cells has great potential for application in regenerative medicine. This project aimed to define effective methods of multipotent stem/stromal cell extraction from adipose tissue (ASC), their expansion and differentiation ex vivo, as well as the examination of their survival and proliferation upon cryopreservation. In addition, the characteristics of ASCs propagated ex vivo were compared in different cell culture model systems, including cultivation in bioreactors and 3D tissue cultures on biomaterial scaffolds. Also, the important aim of this project included investigations of ASCs effects on the proliferation of various tumor cell lines with special emphasis on the maintenance of ASCs biological characteristics and immunoregulatory properties during long-term culture expansion procedures in order to confirm the safety of their clinical use.

Тип пројекта:

International Projects

Role of IL-6/NF-κB/HIF-1 axis in adipose tissue mesenchymal stromal cells-mediated breast cancer cells stemness

Project leader : Dr Trivanović Drenka

Project collaborators:

Dr Aleksandra Jauković, dr Ivana Okić-Đorđević, dr Tamara Kukolj

Project number: SK-SRB-2016-0031

Duration of the project: 2017- 2018

Leading Institution:

Description of the project:

Mesenchymal stromal/ stem cells (MSC) from adipose tissue play an important role in the tumor microenvironment of breast cancer, but the molecular basis of their participation in the regulation of tumor development and progression is insufficiently studied. Persistent inflammation and hypoxia in tumor tissue contribute to the development of cancer stem cells and tumor progression, where transcription factors NF-κB and HIF-1 cooperate to govern the cancer progression.
In order to define potential new targets for the development of antitumor therapeutic strategies, this project aimed to define molecular mechanisms underlying the influence of adipose tissue MSC on stemness properties of breast tumor cells with a special focus on the participation of IL-6/NF-κB/HIF-1 signaling pathway. For these purposes, the effects of MSC adipose tissue or their produced factors on breast tumor cell line MDA-MB-231 were analyzed in terms of mammospheres formation, expression of pluripotency markers, cell cycle/silencing, and modification of NF-κB and/or HIF-1 activation.

Тип пројекта:

International Projects

New therapeutic strategies for reconstruction of bone defects with optimized RIA-derived autologous grafts and bone substitute materials

Project leader: dr Herrmann Marietta

Project collaborators:

Aleksandra Jauković, Ph.D. (coordinator of the work package WP3 and proof-of-concept with 3D Republika), Kukolj Tamara, Ph.D., Hristina Obradović, Ph.D., Milena Živanović, PhD student

Project number: 01DS21004

Duration of the project: July 2021 – June 2024

Leading Institution: University Hospital Würzburg

Description of the project:

Large bone defects present a common clinical problem where autologous bone grafting is the current gold standard. Autologous bone grafts harvested by the Reamer-Irrigator-Aspirator® (RIA) technique are considered advantageous in terms of larger quantities of graft material and yielding two fractions – a solid graft usually used for the transplantation and a liquid fraction often referred to as a waste material. This highly translational project aims to address the regenerative potential of RIA liquid fraction through in vitro studies of its secretory and cellular content as well as by testing pre-conditioning strategies to improve RIA grafts regenerative potential. Also, the project will provide evidence for the new application possibility of bone substitute material PerOssal® (Osartis GmbH) in combination with RIA-graft material. In vitro experiments will be translated into preclinical and clinical trials in Serbia to optimize currently available therapies. In parallel, proof-of-concept experiments with 3D printing materials will be accomplished with the industrial partner from Serbia 3D Republika d.o.o.

Тип пројекта:

International Projects