Abstract
Mesenchymal Stromal Cells (MSC) are promising therapies for fracture healing. However, undifferentiated MSC may act only through an inductive paracrine effect without direct bone formation. Here, we developed an injectable product constituted of human bone-forming cells derived from bone marrow (BM)-MSC (ALLO-P2) that display more potent bone repair properties not only by stimulating host osteoinduction but also by direct bone formation. In vitro, ALLO-P2 overexpressed markers such as ALP compared to BM-MSC isolated from the same donors, suggesting their engagement into the osteogenic lineage. In vivo, a single dose of ALLO-P2 significantly enhanced bone neoformation 14 days post-administration over the calvaria of NMRI-Nude mice compared to the control excipient. Histological analyses and mouse/human type I collagen double-immunolabelling revealed the presence of mineralized bone nodules of mixed host and donor origins in mice administered with ALLO-P2. Together, these results show that ALLO-P2 is a potential promising clinical candidate to promote bone repair, since it can be produced at high yields, is injectable and boosts ossification mechanisms involved in the physiological repair process.
