Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation.
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 transplantation.
d'Aquino
R
R
Dipartimento di Discipline Odontostomatologiche, Ortodontiche e Chirurgiche, Università Secondo Ateneo di Napoli, Napoli, Italy.
Graziano
A
A
Sampaolesi
M
M
Laino
G
G
Pirozzi
G
G
De Rosa
A
A
Papaccio
G
G
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000328:Adult; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D010012:Osteogenesis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D018800:Thy-1 Antigens; D018799:Intercellular Adhesion Molecule-1; D019009:Proto-Oncogene Proteins c-kit