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  • Periodic Report Summary 2 - GLOWBRAIN (Combining Stem Cells and Biomaterials for Brain Repair - Unlocking the Potential of the Existing Brain Research through Innovative In Vivo Molecular Imaging)
FP7

GlowBrain Report Summary

Project reference: 316120
Funded under: FP7-REGPOT

Periodic Report Summary 2 - GLOWBRAIN (Combining Stem Cells and Biomaterials for Brain Repair - Unlocking the Potential of the Existing Brain Research through Innovative In Vivo Molecular Imaging)

Project Context and Objectives:
The main objective of the proposed project GlowBrain is to upgrade and unlock the existing excellence in brain research with specific twist in activities based on development of stem cell and biomaterials applications.
The core idea of this project is based on combined biomaterials and stem cell applications in the brain monitored by combined bioluminescent imaging (BLI) and magnetic resonance imaging (MRI). This would allow to enhance the stem cell delivery and integration in the brain and to monitor both the stem cells and their effects in the living animals. The institutional capacities would be upgraded and a highly needed added value will be obtained in order to achieve the top-notch research organized in a unique way, not present elsewhere in Europe. Exchange of know-how with institutions with proved excellence in applicable science and patenting will open a new dimension enabling the progress in development of innovations and protection of intellectual property.
Our main S&T objective is to introduce a novel approach for stem cell based therapy of nervous system. This will be achieved by using the biomaterials to enhance and control stem cells, and by in vivo monitoring of stem cell behavior after transplantation through complementary combination of two imaging modalities - bioluminescent imaging (BLI) and magnetic resonance imaging (MRI). In order to decrease the most common obstacle in stem cell applications, low survival and integration rate of cells faced with hostile environment, we will use innovative biomaterials which will support formation of 3D cellular networks.
BLI would be used to in vivo monitor gene activity in the brain and in the transplanted stem cells. To visualize through BLI the transgenic animals should be used, already carrying luciferase as bioluminescence reporter under promoter of genes relevant to the brain repair and regeneration. Many of these lines are already present in our facility or in the facilities of our Partnering Organizations.
MRI would be used to in vivo precisely localize transplanted stem cells in the brain. Apart from precise anatomical location, MRI will be used to distinguish brain pathology (in particular after ischemic lesion through MCAO) and repair processes in the mouse brain. In order to be visible. The stem cells should be marked by appropriate particles adhered to the cell surface and visible by MRI, like ultra-small superparamagnetic iron oxide (USPIO). This allows to track the complete transplanted stem cell population and to assess their distribution within the brain.
The advantage of combination of BLI and MRI is that the brain can be visualised both by luciferase markers and superparamagnetic particles. This could enable visualization of the brain by MRI and characterization of its reaction by luciferase as gene expression marker by BLI.
The proof of concept will be establishing the whole procedure of in vivo molecular imaging of transplanted biomaterials-supported stem cells in the mouse brain after MCAO-induced ischemic injury. The setup of such a complete capacities upgrade is very complex and would be based on our previous knowledge and abilities, combined with twinning and exchange of know-how with our partners.
The ability to visualize the brain in the living animals would represent a leading edge asset, which together with all other already existing expertise would establish the highly versatile platform for stem cell research in the brain.

Project Results:
The GlowBrain is based on three pillars: stem cells, biomaterials and in vivo imaging. The activities of GlowBrain established these three pillars and organized them in the joint platform providing innovative approach to study brain diseases in particular the stroke. This platform is now assembled, and its functionality can evolve in the future.
The exchange of know-how and experience with 7 Partnering Organizations was achieved by secondements and expert visits. The training topics included stem cell culture, labeling and transplantation, synthesis and applications of innovative biomaterials, visualizing brain and stem cells with BLI and MRI, and using small animals as disease models in neuroscience. This exchange of knowledge and skills was complemented by 3 Workshops organized in Zagreb, “Stem Cell Techniques” May 23 –25, 2013, “Application of biomaterials and in vivo imaging in stem cell research” from March 27 –29, 2014, and “Visualization of molecular markers in the brain” January 29-31, 2015 in Zagreb at the premises of the Croatian Institute for Brain Research (CIBR), and the Final Conference entitled “Stem cell and biomaterial applications for brain repair” May 27 – 30, 2015.
We succeeded to attract appropriate candidates and give jobs to 11 current GlowBrain employees. Five of them held their previous positions abroad, 4 of them were Croatian returnees, 6 of them are women. The GlowBrain employees include 9 experienced scientists, 1 person dedicated to the innovation management, and 1 administrative officer. Instead of originally planned 8 positions, with the same resources we achieved to open 11.
The in vivo imaging platform was assembled in a completely renovated laboratory. The new laboratory is currently the only preclinical laboratory at the institutions fulfilling all the requirements of the light, ventilation, air conditioning, sound, cleanness (BSL2) appropriate for the envisaged work. The acquired instruments, preclinical optical imager Perkin Elmer IVIS Spectrum and preclinical MR scanner Bruker 20/70 USM are top of the class instruments and probably the top in sense of best buy and versatility categories. The animal facility was upgraded and the conditions improved.
The Innovation Office and Innovation Manager achieved substantial collaboration with the corresponding University structures, and with IP experts in Croatia and abroad. The permanent collaboration with the experts in the field was established. The visits to the Partnering Organisations in relation to the IP policies were accomplished and the analysis of both their IP capabilities and the capabilities of our own institution provided. This influenced the institution to set up the Committee on intellectual property management, and approve the official document Policy on Intellectual Property Management.
GlowBrain was in particular successful in dissemination and promotional activities. In order to help the development of the emerging stem cell therapies GlowBrain continued the activities of the RegMed – Regional Network for Regenerative Medicine and Stem Cell Therapies, which gathered the experts form different disciplines, from basic researchers to clinicians, lawyers, enterpreneurs, industry representatives and ethic experts. The activities of GlowBrain were shown through its web page, Facebook and YouTube profile. Promotional movies were continued to be made to explain GlowBrain. The two public events “The Night(s) when Brains are Glowing” were organized as a major promotional event of GlowBrain and it increased visibility of GlowBrain activities to professional community, politicians, celebrities, and general public. As a consequence GlowBrain received wide coverage of media, and attracted the considerable attention in Croatia.
The project website is http://glowbrain.hiim.hr/.
The Facebook profile is https://www.facebook.com/GlowBrainCroatia.
The YouTube movies are http://www.youtube.com/results?search_query=glowbrain

Potential Impact:
The expected final result of the project is fully functional GlowBrain platform. This platform includes following expertise: stem cell isolation, in vitro culture of stem cells, synthesis of biomaterials, analyses of cell behavior on biomaterials` surfaces, in vitro differentiation of stem cells, monitoring of differentiation by molecular analysis and immunohistochemistry, genetic modification of stem cells, enhancing the stem cell properties by biomaterial application, labeling of stem cells, experimental stroke model in mice (medial cerebral artery occlusion, MCAO), monitoring of the consequences of stroke model, applying bioluminescent imaging and magnetic resonance imaging on the mouse stroke model, combining the two modes of imaging on the same animal, transplantation of the stem cells with or w/o biomaterial supports,
monitoring the consequences of stem cell transplantation, visualizing the stem cells in the mouse brain by in vivo imaging, analyzing the combined data and adjusting the procedure, and using the platform to monitor stem cell and biomaterials application in stroke mouse model.

The expertise of platform is result of secondements, expert visits, workshops and conference. The equipment purchase is completed and equipment installed. In addition the innovation capacities of the institution are upgraded and the IPR strategy developed. The visibility of GlowBrain intends that it be fully recognized as a success story.

The potential impact of GlowBrain would be better integration of Coordinating institution (Universtiy of Zagreb School of Medicine) in the European Research Area as a whole, which includes long lasting partnership with research groups elsewhere in the Europe, in particular with the Partnering Organizations. The upgraded GlowBrain platform would not only serve for neuroscience, but would be a valuable asset for different basic research for the whole University of Zagreb. This should enable to increase scientific production not only of the GlowBrain team, but as well of the whole institution. The regenerative medicine impact of the proposed GlowBrain platform is an important economical asset for the professional community in particular to the partners of RegMed network established through GlowBrain. The obvious way to explore its potential is to transfer stem cell research through translational approach to clinical applications. The environment for this “from bench to bedside” approach will be influenced by GlowBrain activities and results. The final impact of the project will as well depend on its sustainability, which represents a major challenge project needs to face in the near future.

List of Websites:
http://glowbrain.hiim.hr

Contact

Vikic Topic, Smiljka (Head of Office)
Tel.: +385 1 4566972
Fax: +385 1 4566724
E-mail
Record Number: 182354 / Last updated on: 2016-05-23
Information source: SESAM