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Human Postnatal Dental Pulp Cells Co-Differentiate into Osteoblasts and Endotheliocytes: A Pivotal Synergy Leading to Adult Bone Tissue Formation

PRC/D/2007/Mar 15

Cell Death and Differentiation (2007) 14

R d'Aquino, M Sampaolesi, G Laino, G Pirozzi, A De Rosa and G Papaccio

Dipartimento di Discipline Odontostomatologiche, Ortodontiche e Chirurgiche, Universita` Secondo Ateneo di Napoli, Napoli, Italy; Dipartimento di Medicina Sperimentale, Sezione di Istologia ed Embriologia, Universita` Secondo Ateneo di Napoli, Napoli, Italy; DIBIT Dipartimentale San Raffaele Scientific Institute, Universita` Vita e Salute, Stem Cell Research Institute, Milan, Italy and UOS Dipartimentale, Diagnostica Molecolare, Analisi d'immagine e citometrı´a a flusso, Istituto Nazionale Tumori 'G. Pascale', Napoli, Italy

Stromal stem cells from human dental pulp (SBP-DPSCs) were used to study osteogenic differentiation in vitro and in vivo. We previously reported that SBP-DPSCs are multipotent stem cells able to differentiate into osteoblasts, which synthesize three dimensional woven bone tissue chips in vitro. In this study, we followed the temporal expression pattern of specific markers in SBP-DPSCs and found that, when differentiating into osteoblasts, they express, besides osteocalcin, also flk-1 (VEGF-R2). In addition, 30% of them expressed specific antigens for endothelial cells, including CD54, von-Willebrand (domain 1 and 2), CD31 (PECAM-1) and angiotensin-converting enzyme. Interestingly, we found endotheliocytes forming vessel walls, observing that stem cells synergically differentiate into osteoblasts and endotheliocytes, and that flk-1 exerts a pivotal role in coupling osteoblast and endotheliocyte differentiation. When either SBP-DPSCs or bone chips obtained in vitro were transplanted into immunocompromised rats, they generated a tissue structure with an integral blood supply similar to that of human adult bone; in fact, a large number of HLA-1 + vessels were observed either within the bone or surrounding it in a periosteal layer. This study provides direct evidence to suggest that osteogenesis and angiogenesis mediated by human SBP-DPSCs may be regulated by distinct mechanisms, leading to the organization of adult bone tissue after stem cell transplantion.

Cell Death and Differentiation (2007) 14,1162-1171.doi:10.1038/sj.cdd.4402121;published online 9 March 2007


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