Human DPSCs fabricate vascularized woven bone tissue: a new tool in bone tissue engineering

Human dental pulp stem cells (hDPSCs) are mesenchymal stem cells successfully used in human bone tissue engineering. To better establish if these cells can lead to a bone tissue ready to be grafted, we checked DPSCs for their osteogenic and angiogenic differentiation capabilities with the specific aim to obtain a new tool for bone transplantation. Therefore, hDPSCs were specifically selected from the stromal-vascular dental pulp fraction, using appropriate markers and cultured. Growth curves, expression of bone-related markers, calcification, angiogenesis as well as in vivo transplantation assay were performed. We found that hDPSCs proliferate, differentiate into osteoblasts and express high levels of angiogenic genes such as VEGF and PDGFA. hDPSCs, after 40 days of culture, give rise to a 3D structure resembling a woven fibrous bone. These Woven Bone (WB) samples were analyzed by classical histology and Synchrotron-based X-ray phase-contrast microtomography and holotomography. WB showed histological and physical attractive qualities of a bone with few areas of mineralization and neo-vessels. Such WB, when transplanted in rats, was remodeled into a vascularized bone tissue. Taken together our data lead to the assumption that WB samples, fabricated by DPSCs, constitute a noteworthy tool do not requiring the use of scaffolds, therefore being ready for custom regeneration.