Projects

Harnessing H₂S to Induce a Hibernation-Like State in Mesenchymal Stromal Cells as a Strategy for Efficient Non-Freezing Cell Preservation

Duration of the project: 2025-2026.

Description of the project:

Mesenchymal stromal cells (MStroC) represent one of the most promising tools in regenerative medicine due to their regenerative and immunomodulatory properties. However, their clinical application is limited by significantly reduced survival and functionality after cryopreservation, which highlights the need to improve their storage strategies before transplantation. The main objective of this project is to develop an innovative, non-cryogenic method for MStroC preservation by using a hydrogen sulfide (H₂S) donor to induce a state of low metabolic activity similar to hibernation, thereby protecting cells from cold stress during short-term storage at 4°C, while preserving their viability, regenerative and immunomodulatory potential upon rewarming. Through the collaboration of a Serbian and French team, the project aims to create a new and efficient platform for short-term storage of MStroC at 4°C. This approach would enable better preparation, transport, and clinical application of MStroC as advanced therapeutic products (ATMPs) in regenerative medicine and cell therapies.

 

Тип пројекта:

Bilateral Scientific Cooperation

Platform for Ex Vivo Growth of Patient-Specific Multiple Myeloma Cells in a Native-Like Microenvironment: Towards Xeno-Free Production on Demand (PERSONAE)

Description of the project:

Multiple myeloma (MM), an incurable cancer of the bone marrow plasma cells, is the second most frequent hematological malignancy. Despite growing number of approved therapeutics, proliferative clonal myeloma plasma cells (MPCs) persist in bone marrow, even in patients where minimal residual disease (MRD) is not evident. Existing treatment options are generalized, often ineffective, and highly toxic, emphasizing the urgency for personalized oncology development. However, no bone marrow in vitro drug testing system has been available for extensive drug response assessment. This project aims to develop a miniaturized, xeno-free platform that mimics the myeloma bone marrow microenvironment for the growth of patient-specific MPCs using human platelet-released factors, adjusted oxygen levels, and patient-derived mesenchymal stromal cells as feeder layers. MPC quality is monitored through immunophenotype, proliferation, clonality, and DNA index analyses. The platform targets high-throughput, low-cost anti-myeloma drug screening and personalized response prediction for use in biopharma, clinical research, and healthcare settings, with a defined commercialization strategy at local and global levels.

Тип пројекта:

Proof of Concept

Determining the Potential of Placental Tissue Derivatives for Use in Post-Mastectomy Breast Reconstruction: Development of a 3D-Printed Bioscaffold (AmnioPrintCare)

Project leader: Dr. Hristina Obradović

Project collaborators: Dr. Ivana Okić Đorđević, Dr. Sanja Momčilović, Dragana Aleksandrović, Dr. Ivana Gazikalović (external team member), Dr. Nikola Jeftić (external team member)

Project number: 11073

Duration of the project: 2024-2026.

Leading institution: Institute for Medical Research, University of Belgrade

Collaborating institutions: Innovation Center, Faculty of Technology and Metallurgy, University of Belgrade, Institute for Oncology and Radiology of Serbia

Description of the project:

Despite their safety and feasibility for patients, existing breast reconstruction techniques following mastectomy carry the risk of potential complications, and do not significantly alter the likelihood of disease recurrence compared to mastectomy alone. Hence, these factors must be considered when evaluating the available breast reconstruction options post-mastectomy. The field of tissue engineering has been intensively growing primarily focusing on crafting diverse scaffolds that act as templates for tissue regeneration. For nearly a century, the amniotic membrane (AM) of the placenta has been utilized in skin and cornea regeneration, and numerous studies have demonstrated its antitumor, antifibrotic, antiinflammatory, and immunomodulatory properties. AmnioPrintCare aims to develop the scaffold biomaterial using human AM homogenate that will preserve and exhibit its regenerative and antitumor effects over an extended period when applied. By establishing advanced 3D bioprinting techniques for scaffold fabrication, AmnioPrintCare will enable more accessible and personalized regenerative medicine practices in breast reconstruction. To achieve that, by using different technological methods and advanced 3D software and bioprinter, we will establish 3D printed bioscaffold based on hAM. Also, we will confirm its biocompatibility with the breast tissue niche cells and its regenerative potential in vitro related to adipogenesis and angiogenesis along with the antitumor effect towards breast cancer cell lines. We will further evaluate its regenerative and antitumor effect upon transplantation in mice. This interdisciplinary project will bring advancement in biotechnology that will lead to improvements in biomedicine and provide basis for better healthcare and survival rate among patients, novelties in the medical and biotechnological education, and improvement of biotech industry in Serbia as it could patent the new ‘’bioink’’ for commercially available bioprinters.

Тип пројекта:

National Projects

Development of Mucoadhesive Films with Amniotic Membrane Homogenate for Potential Application in Oral Tissue Regeneration

Project leader: Dr. Ivana Okić Đorđević

Project collaborators: Dr. Hristina Obradović, Dr. Drenka Trivanović, Dr. Ivana Drvenica, Dr. Sanja Momčilović

Project 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:

Bilateral Scientific Cooperation

Development of a Raman Spectroscopy Method for Estimating the Regenerative Potential of Mesenchymal Stem Cells at the Single-Cell Level

Project leader: Dr. Tamara Kukolj

Project collaborators: Dr. Jasmina Lazarević, Dr. Uroš Ralević, Dr. Nenad Lazarević from Institute of Physics, University of Belgrade

Project number: “Start up for science” 2019/2020 funded by Philip Morris Company

Duration of the project: 2019-2020.

Leading institution: Institute for Medical Research, University of Belgrade

Description of the project:

Analysis of the characteristics of mesenchymal stem cells (MSCs) at the level of individual cells using Raman spectroscopy with the aim of developing Raman spectroscopy as a fast, simple, and non-destructive Single Cell method for evaluating the regenerative potential of MSCs. Most biochemical changes, caused by physiological or pathological changes, are observed in the Raman spectrum under appropriate conditions, as a change in the intensity and/or position of the Raman mode. Therefore, the characteristics of MSCs originating from different tissues and donors will be investigated, as well as changes in age-related characteristics in MSCs populations. Changes in the Raman spectrum resulting from replicative age, i.e. prolonged cultivation in vitro, will be monitored, as well as changes in the spectrum caused by certain pharmacological substances used in the therapy of various diseases, which accelerate the aging process. Based on the obtained results, the correlation between the vibrational spectrum and the regenerative potential of primary MSCs will be determined, which will enable the establishment of Raman spectroscopy as a fast, simple, and non-invasive method for the qualitative analysis of the regenerative potential of a certain population of MSCs. This project will contribute to the detailed characterization of MSCs, to significantly speed up and facilitate their further application in cell therapy and tissue engineering.

Тип пројекта:

National Projects

Establishment of an ALPL Gene-Deficient Patient-Derived Cell Line for Investigation of the Metabolic Background of Hip Osteoarthritis

Project leader: Dr. Drenka Trivanović

Project collaborators: Dr. Slavko Mojsilović, Dr. Ivana Okić Đorđević, Dr. Aleksandra Jauković, Dr. Tamara Kukolj, Dr. Hristina Obradović, Dr. Anđelija Petrović, Milena Živanović

Project number: Q422RSV70

Duration of the project: January 2023-December 2023.

Leading institution: Institute for Medical Research, University of Belgrade

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. 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

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
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