Although there is great interest in the new knowledge economy, less favoured regions seem permanently disadvantaged because they lack a critical mass of knowledge capital to initiate accumulation, growth and economic development processes. This is a problem for policy-makers seeking to promote economic growth and territorial cohesion in such regions. Despite this, examples from two such regions, Newcastle, UK and Twente, the Netherlands, suggests that such companies can be very successful. This paper seeks to develop a conceptual model of how university spin-off companies (USOs) can improve their regional economies. The economic benefits that such companies bring are explored, to identify, those elements which can potentially upgrade regional economies through knowledge accumulation, which are termed 'building up territorial knowledge pools'. This paper concludes by developing a conceptual framework for the operation of the territorial knowledge pool; highlighting four different roles played by USOs in improving regional innovation environments and considering the conceptual and policy implications raised by the framework model.