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Nowadays innovation challenges in cities can be solved only through collaboration between different players: government, business, citizen and finally SMEs. The purpose of the “Start-ups for cities” Project is to help cities/territories/regions to get results out of their open innovation programs. Startups are the way that global cities are going to be able to adopt a new smart approach. Start-ups play a pivotal role in driving the “smart” technology sector forward.To unlock the potential of open innovation cities need to focus on global tech talents attraction and retention, in other words to organize new formats of communication/integration with start-ups and involve them, as active player, in smart cities development.