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Metabolic Effects of Bone Marrow Adipose Tissue on Multiple Myeloma

Project leader: Dr. Drenka Trivanović

Project collaborators: Dr. Ivana Okić Djordjević, Dr. Aleksandra Jauković, Dr. Marijana Kovačić, Dr. Sanja Momčilović, Milena Živanović

Project number:

Duration of the project: 2023-2024.

Leading institution: Julius-Maximilians-Universität Würzburg – Department for Musculoskeletal Tissue Regeneration

Collaborating institution: Institute for Orthopedic Surgery “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:

Bilateral Scientific Cooperation

Interaction Between the Transcription Factor p53 and the Wnt Signaling Pathway in the Maintenance of Stemness in Mesenchymal Stem Cells

Project leader: Dr. Jelena Krstić

Project collaborators: Dr. Drenka Trivanović, Dr. Hristina Obradović, Dr. Tamara Kukolj, Dr. Ivana Okić Đorđević

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

Duration of the project: 2016-2017.

Leading institution: Institute for Medical Research, University of Belgrade

Collaborating institution: Medical Faculty, University of Graz

Description of the project:

Stem cell self-renewal and differentiation are tightly regulated processes that contribute to the maintenance of tissue homeostasis. The transcription factor p53 is known to regulate these processes in embryonic and adult stem cells in a dual manner through 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 derived from perinatal tissues, including the umbilical cord and amnion, was investigated. For this purpose, the expression of pluripotency markers (Nanog, Sox2, Oct4) and markers of adipogenic/osteogenic differentiation potential (PPARγ, adiponectin, Runx2, osteocalcin) was analyzed in mesenchymal stem cells from perinatal tissues. Conditions of induced or suppressed p53 expression in these cells were established using gene transfection methods or specific pharmacological activators/inhibitors, including nutlin and pifithrin.

Тип пројекта:

Bilateral Scientific Cooperation

Human Culture-Expanded Adipose Stromal/Stem Cells: Serial Expansion and Maintenance of Their Proliferative, Multipotent, and Regulatory Properties

Project leader: Dr. Aleksandra Jauković

Project collaborators: Dr. Diana Bugarski, Dr. Jelena Kocić, Dr. Drenka Trivanović

Project number: 451-03-02338/2012-14/05

Duration of the project: 2013-2014.

Leading institution: Institute for Medical Research, University of Belgrade

Collaborating institution: Department of Bioengineering, Instituto Superior Técnico (IST), Tecnical University of Lisbon

Description of the project:

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:

Bilateral Scientific Cooperation

Building an Open European Network on Osteoarthritis Research

Project leader: Dr. Corne Baatenburg de Jong

Project collaborator: Dr. Drenka Trivanović

Project number: CA21110

Duration of the project: October 2022-October 2026.

Leading institution: Stichting ReumaNederland, Amsterdam, the Netherlands

Description of the project:

The main aim of NetwOArk is to set up the European Society for Osteoarthritis (ESOA), with three major stakeholder groups, 1) patients, 2) clinicians and 3) researchers, both from academia and industry. The COST Action will allow us to start the process of building such a European Society, with the aim of coordinating and stimulating more interdisciplinary and transdisciplinary research, technological development and translation of the results to the clinic, aimed at improving the quality of life of those affected by osteoarthritis in Europe. The areas to be addressed in this Action are Primary prevention, Diagnostics, Treatment, Interaction (comorbidities) and Care Management. EU-netwOArk aims to boost new scientific breakthroughs on the five main osteoarthritis themes.

Тип пројекта:

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Role of the IL-6/NF-κB/HIF-1 Axis in Adipose Tissue Mesenchymal Stromal Cell-Mediated Stemness of Breast Cancer Cells

Project leader: Dr. Drenka Trivanović

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: Institute for Medical Research, University of Belgrade

Collaborating institution: Institute for Cancer Research, Slovak Academy of Sciences

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:

Bilateral Scientific Cooperation

Genome Editing to Treat Human Diseases

Project leader: Dr. Karim Benabdellah

Project collaborators: Dr. Drenka Trivanović (MC member), Dr. Aleksandra Jauković, Dr. Sanja Vignjević Petrinović, Dr. Ivana Drvenica

Project number: CA21113

Duration of the project: September 2021-September 2025.

Leading institution: Fundación Pública Andaluza, Progreso y Salud, Granada, Spain

Description of the project:

Recent advances on genome editing technologies have opened the possibility of treating diseases through precise modifications of patients’ genomes. However, the translation of the genome editing technologies to address public health needs, require a strong collaboration between basic and clinical research, regulatory bodies and the different stake holders involved for each application. There are several networks to improve or analyse genome editing technologies for different applications, however, no one cover all the actors involved in gene therapy translation. The principal aim of the GenE-HumDi Action is to bring together pharmaceutical companies, academic institution, science and regulatory agencies, biotechnology firms, patient advocacy association and information technology, in order to tackle knowledge fragmentation with the aim to accelerate the translation of GE technologies to the treatment of human diseases.

Тип пројекта:

Cost

New Therapeutic Strategies for the Reconstruction of Bone Defects Using Optimized RIA-Derived Autologous Grafts and Bone Substitute Materials (RIABONE)

Project leader: Dr. Marietta Herrmann, Dr. Aleksandra Jauković

Project collaborators: Dr. Tamara Kukolj, Dr. Hristina Obradović, Milena Živanović

Project number: 01DS21004

Duration of the project: July 2021-June 2024.

Leading institution: University Hospital in Würzburg, Germany

Collaborating institutions: Institute for Medical Research, University of Belgrade, Institute of Orthopedics ”Banjica”, Faculty of Veterinary Medicine, University of Belgrade

Collaborating companies: Osartis GmbH, Germany, 3D Republika d.o.o., Serbia

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

The European Network for Stem Cell Core Facilities (CorEuStem)

Project leader: Dr. Laura Batlle Morera

Project collaborators: Dr. Aleksandra Jauković (MC member), Dr. Ivana Okić Đorđević, Dr. Slavko Mojsilović, Dr. Tamara Kukolj

Project number: CA20140

Duration of the project: October 2021-October 2025.

Leading institution: Center for Genomic Regulation, Barcelona, Spain

Description of the project:

CorEuStem is formed upon recognizing the need to connect core facilities in European research centers and universities that provide services in such fields as disease modelling, embryology, and novel regenerative therapeutic approaches, to keep track of all advancements in cutting-edge technologies. This network is composed of experts in stem cell, differentiation, organoids, and gene editing technologies with the aim of joining forces and establishing the first European network for harmonizing procedures and protocols, to organise joint training schools for implementing new cutting-edge technologies emerging in the field and to become a reference point in stem cells, differentiation, organoids and gene editing in Europe and beyond. The IMR team, having extensive experience in adult stem cell research, has embraced the opportunity to become a part of this network of experts, hoping of both gaining insights in emerging technologies and providing a competent input to the consortium.

Тип пројекта:

Cost

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