Physico-mechanical programming of stem cells for regenerative medicine
Due to demographic and lifestyle changes, traumatic injuries and inflammatory diseases have grown to become paramount medical and socio-economic challenges in industrialized nations. The success of the available cells therapies relies largely on their regenerative potential, which is anticipated to vary with age and disuse. There is a need of a new generation of innovators able to develop transformative approaches to stem cell manipulation to accelerate their translation into clinical practice. So far, biochemical treatments with soluble factors are still the gold standard to induce and direct stem cell differentiation towards a specific lineage. This approach has, however, limitations mostly related to its costs, possible side effects, upscaling challenging and finally lack of innovation. Our scientific approach entails the combined use of materials (e.g., nanofibrillar cellulose, calcium phosphates, hydrogels) and their nano-, and microfabrication techniques together with physical stimulation to direct and monitor both stem cell fate and secretory activity. The key innovative aspect of the project resides in the combination of advanced physico-mechanical stimuli (e.g., topographic, vibrational and electric stimuli) tackling the need for a process that can guarantee large amounts of differentiated and effective cells for their use in a clinical setting. Moreover, highly sensitive sensors will be developed and adopted to monitor the release of specific cytokines secreted informing on differentiation state and regenerative potential. They will allow us to modulate the stimulation protocols and to optimize the procedures in a simpler, more convenient, and thorough way. A proof of concept of a cell-processing factory will be developed to test the efficacy of the strategies combining stem cells and stimulation protocols. The cross-disciplinary consortium will integrate the different and complementary technologies and know-hows from the partners’ laboratories. The consortium will bring together the expertise in stem cell biology, sensor development, bioelectronics, piezoelectric materials, microfluidics, macro- and nanofabrication as well as physical stimulation to deliver a multi-modular integrated lab-scale cell process factory to study and investigate stem cell fate in response to the investigated materials and physical stimuli. The project will lead to the creation of transformative knowledge in guiding adult stem cell fate for biomedical applications. It will allow the establishment of innovative, integrated approach towards the production, stimulation, and control of stem cells that will benefit both the academic and the industrial world. Thanks to the MRSEI-ANR call, an European consortium will be built that will mentor and train a new generation of Scientists/Innovators providing advanced knowledge and skills in physics, materials, manufacturing, and stem cell biology. These areas rarely combined together, will lead to the development of innovative tools to support breakthrough advances in the technologies allowing manipulation of stem cells for clinical applications. Novel training programs will be developed together with the clinical and industrial partners allowing PhD candidates to enrich and nurture their skills and step outside academia, in particular in industry and business.
Due to demographic and lifestyle changes, traumatic injuries and inflammatory diseases have grown to become paramount medical and socio-economic challenges in industrialized nations. The success of the available cells therapies relies largely on their regenerative potential, which is anticipated to vary with age and disuse. There is a need of a new generation of innovators able to develop transformative approaches to stem cell manipulation to accelerate their translation into clinical practice. So far, biochemical treatments with soluble factors are still the gold standard to induce and direct stem cell differentiation towards a specific lineage. This approach has, however, limitations mostly related to its costs, possible side effects, upscaling challenging and finally lack of innovation. Our scientific approach entails the combined use of materials (e.g., nanofibrillar cellulose, calcium phosphates, hydrogels) and their nano-, and microfabrication techniques together with physical stimulation to direct and monitor both stem cell fate and secretory activity. The key innovative aspect of the project resides in the combination of advanced physico-mechanical stimuli (e.g., topographic, vibrational and electric stimuli) tackling the need for a process that can guarantee large amounts of differentiated and effective cells for their use in a clinical setting. Moreover, highly sensitive sensors will be developed and adopted to monitor the release of specific cytokines secreted informing on differentiation state and regenerative potential. They will allow us to modulate the stimulation protocols and to optimize the procedures in a simpler, more convenient, and thorough way. A proof of concept of a cell-processing factory will be developed to test the efficacy of the strategies combining stem cells and stimulation protocols. The cross-disciplinary consortium will integrate the different and complementary technologies and know-hows from the partners’ laboratories. The consortium will bring together the expertise in stem cell biology, sensor development, bioelectronics, piezoelectric materials, microfluidics, macro- and nanofabrication as well as physical stimulation to deliver a multi-modular integrated lab-scale cell process factory to study and investigate stem cell fate in response to the investigated materials and physical stimuli. The project will lead to the creation of transformative knowledge in guiding adult stem cell fate for biomedical applications. It will allow the establishment of innovative, integrated approach towards the production, stimulation, and control of stem cells that will benefit both the academic and the industrial world. Thanks to the MRSEI-ANR call, an European consortium will be built that will mentor and train a new generation of Scientists/Innovators providing advanced knowledge and skills in physics, materials, manufacturing, and stem cell biology. These areas rarely combined together, will lead to the development of innovative tools to support breakthrough advances in the technologies allowing manipulation of stem cells for clinical applications. Novel training programs will be developed together with the clinical and industrial partners allowing PhD candidates to enrich and nurture their skills and step outside academia, in particular in industry and business.

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