Tissue Engineering and Regenerative Medicine

It is known that progenitor cells undergo an age-dependent decline in their number and function resulting in tissue aging and disease. Since their ex vivo isolation has been introduced in regenerative medicine, these impairments may limit stem cells performance ex vivo and possible after transplantation. Therefore, we considered that the identification of possible molecular fingerprints driving aging can contribute in better age-related disease understanding and in generating tools to favor ex vivo progenitor performance for improved therapeutic benefits. Starting from an age-related comparison of a know stem cell type, we identified aged progenitor- specific miRNA signature that involves only 7 microRNA. Focusing on their targets, we selected HOXB7 as age related gene and whose expression was inversely correlated with senescence. Forced HOXB7 expression was associated with an improved cell growth, a reduction of senescence and an enhanced osteogenesis, linked to a dramatic increase of autocrine bFGF secretion. Based on these original observations we proposed an ex vivo HOX-based reprogramming strategy aimed to empowering key features of mesenchymal adult progenitors for innovative approaches of tissue regeneration and repair.