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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

Genome Editing to Treat Humans Diseases

Project leader: Karim Benabdellah

Project collaborators:

Drenka Trivanović (MC member), Aleksandra Jauković, Sanja Vignjević-Petrinović, Ivana Drvenica

Project number: CA21113

Duration of the project: September 2021. – September 2025.

Leading Institution: Fundación Pública Andaluza, Progreso y Salud, Granada, Španija

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:

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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

The European Network for Stem cell Core Facilities

Project leader : Laura Batlle Morera

Project collaborators:

Aleksandra Jauković (MC member), Ivana Okić Đorđević, Slavko Mojsilović, Tamara Kukolj

Project number: CA20140

Duration of the project: October 2021 – October 2025

Leading Institution: Center for Genomic Regulation, Barselona, Španija

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.

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Regenerative and modulatory potential of adult stem cells

Project leader: Diana Bugarski

Project collaborators:

Aleksandra Jauković, Slavko Mojsilović, Drenka Trivanović, Ivana Okić Đorđević, Tamara Kukolj, Hristina Obradović, Jelena Krstić, Juan F. Santibañez, Sanja Vignjević Petrinović, Sanja Momčilović, Irina Maslovarić

Project number: OI 175062

Duration of the project: January 2011 – December 2020

Leading Institution: Институт за медицинска истраживања, Универзитет у Београду

Description of the project:

This project aimed to investigate the cellular and molecular aspects of the biology and function of multipotent adult stem cells, specifically hematopoietic stem cells and mesenchymal stromal cells. At the beginning of the project period, mesenchymal stromal cells were isolated and characterized (phenotypically and functionally) from various tissues of human and animal origin, including bone marrow, adipose tissue, umbilical cord, dental pulp, and periodontal ligament. In the following phase, the role and mode of action of various factors, primarily the inflammatory microenvironment, on the functional properties of adult stem cells were investigated, as well as the interaction of mesenchymal stromal cells with hematopoietic, immune, and tumor cells, with a particular focus on their role in immunoregulation and tumorigenesis. This project resulted in over 60 publications and presentations at scientific conferences (including 35 in JCI-indexed journals).

Тип пројекта:

National Projects

Application of Low Temperature Plasmas in Biomedicine, Environmental Control and Nanotechnologies

Project leader: Nevena Puač

Project collaborators: Pavle Milenković, Slavko Mojsilović

Project number: III 41011

Duration of the project: January 2011 – December 2020

Leading Institution: Institute of Physics, UB

Description of the project:

This interdisciplinary project aimed to develop a new system of cold atmospheric plasma for use in biomedicine, environmental control, and nanotechnology. It consisted of four sub-projects: 1) Atmospheric discharges, 2) Plasma application in biology and medicine, 3) Plasma application in positron diagnostics, nanotechnology, and material functionalization, and 4) Measurements of biogenic volatile organic compounds. Institute for Medical Research participated in the second sub-project, led by Professor Pavle Milenković. Within this sub-project, the impact of cold atmospheric plasma on the regenerative properties of human dental-derived mesenchymal stromal/stem cells was investigated, both in vitro and in vivo (the rabbit calvarial critical-size defect model). The result of this sub-project was the publication of several papers in prestigious scientific journals and presentations at numerous international conferences.

Тип пројекта:

National Projects

International Network for Translating Research on Perinatal Derivatives into Therapeutic Approaches

Project leader : Ornella Parolini

Project collaborators: Diana Bugarski, Slavko Mojsilović, Hristina Obradović

Project number: CA17116

Duration of the project: October 2018 – April 2023

Leading Institution: Università Cattolica del Sacro Cuore, Rim, Italija

Description of the project:

This COST action aims to unite a currently fragmented critical mass of academic, clinical, and industry expertise to improve both the fundamental understanding and translational potential of perinatal derivatives. It includes participants with extensive know-how in basic research, clinical trials, regulatory affairs, and biomedical industry. SPRINT is joining forces to strengthen knowledge in the field and overcome the bottlenecks of translation to enable innovative therapeutic applications of perinatal-derived tissues, cells, and factors. Within Action Working Group 2, the IMR team worked to review preclinical studies in animal models to assess the efficacy of therapeutic interventions and identify research gaps, resulting in three papers co-authored by IMR team members.

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