Noggin improves bone healing elicited by muscle stem cells expressing inducible BMP4

The aim of this study was to test the hypothesis that a specific antagonist may enhance the efficacy of its corresponding growth factor in a regulated tissue engineering strategy. Our prior research has led to the development of a retroviral vector that enables optimal regulated bone morphogenetic protein 4 (BMP4) expression in vitro and regulated bone formation in vivo with transduced muscle stem cells. However, when implanted in critical-sized calvarial defects, these cells led to residual bone formation without induction or bone overgrowth with induction, even at reduced cell doses. We thus co-implanted the aforementioned cells with stem cells engineered to express Noggin, a specific BMP antagonist. This approach, while preserving our ability to regulate bone regeneration closely, prevented both the basal level bone regeneration and the bone overgrowth and, more importantly, led to the regeneration of bone that more closely resembled normal bone. We believe that this regulatable tissue engineering strategy, enhanced by utilizing a specific antagonist, constitutes a new paradigm for tissue engineering and regenerative medicine.