Hypophosphatasia and mesenchymal stem cells: a therapeutic promise

Hypophosphatasia (HPP) is due to mutations in ALPL gene which encodes the tissue non-specific alkaline phosphatase isozyme (TNSALP). Defective/inactive TNSALP causes an increased concentration of inorganic pyrophosphate (PPi) in bone matrix that impairs bone mineralization. The accumulation of extracellular PPi observed in HPP causes impairment in bone mineralization process and leads to a disturbance of calcium and Pi homeostasis. The pathogenesis of bone hypomineralization in HPP is relatively well understood; biomedical research aiming to treatment has been focused on the most obvious approach, i.e. enzyme replacement therapy, with unsatisfactory results. More innovative therapeutic approaches can be devised nowadays, thanks to current biotechnological innovations.