Center for Craniofacial Regeneration (CCR), Fu Foundation School of Engineering and Applied Science, Columbia University Medical Center, Columbia University, 630 W. 168 St. – PH7E-CDM, New York, NY 10032, USA.
Dental pulp has intrinsic capacity for self-repair. However, it is not clear whether dental pulp cells can be recruited endogenously for regenerating pulp tissues, including mineralizing into dentin. This work is based on a hypothesis that dental pulp stem/progenitor cells can be induced to migrate by chemotactic cytokines and act as endogenous cell sources for regeneration and mineralization. Dental stem cells (DSCs) were isolated from adult human tooth pulp and seeded on the surfaces of 3D collagen gel cylinders that were incubated in chemically defined media with stromal-derived factor-1α (SDF1), basic fibroblast growth factor (bFGF), or bone morphogenetic protein-7 (BMP7). Significantly more cells were recruited into collagen gel by SDF1 or bFGF than without cytokines in 7 days, whereas BMP7 had little effect on cell recruitment. BMP7, however, was highly effective, equally to dexamethasone, in orchestrating mineralization of cultured DSCs. Cell membrane receptors for SDF1, bFGF, and BMP7 were up-regulated in treated DSCs. Upon in vivo delivery, bFGF induced re-cellularization and re-vascularization in endodontically treated human teeth implanted into the dorsum of rats. Thus, endogenous dental pulp cells, including stem/progenitor cells, may be recruited and subsequently differentiated by chemotaxis of selective cytokines in the regeneration of dental pulp.
"Donor-matched alveolar bone chips were cut into minute pieces per our prior methods (Yang et al. 2010; Suzuki et al. 2011). Both DPCs and ABCs were isolated and cultured in low-glucose Dulbecco's Modified Eagle's Medium (DMEM) (Gibco BRL, OR, USA) containing 10% FBS (fetal bovine serum; Gibco BRL) per our prior methods (Yang et al. 2010; Suzuki et al. 2011). Cells were seeded into 10-cm culture plates with low-glucose DMEM supplied with 10% FBS. "
"SDF-1, as a chemoattractant to host stem cells, has been widely explored in heart, brain, kidney, bone and tooth , –. In this study, we investigated SDF-1 effects on bone formation both ectopically and in critical-sized bone defects. "
[Show abstract][Hide abstract] ABSTRACT: Host blood circulating stem cells are an important cell source that participates in the repair of damaged tissues. The clinical challenge is how to improve the recruitment of circulating stem cells into the local wound area and enhance tissue regeneration. Stromal-derived factor-1 (SDF-1) has been shown to be a potent chemoattractant of blood circulating stem cells into the local wound microenvironment. In order to investigate effects of SDF-1 on bone development and the repair of a large bone defect beyond host self-repair capacity, the BMP-induced subcutaneous ectopic bone formation and calvarial critical-sized defect murine models were used in this preclinical study. A dose escalation of SDF-1 were loaded into collagen scaffolds containing BMP, VEGF, or PDGF, and implanted into subcutaneous sites at mouse dorsa or calvarial critical-sized bone defects for 2 and 4 weeks. The harvested biopsies were examined by microCT and histology. The results demonstrated that while SDF-1 had no effect in the ectopic bone model in promoting de novo osteogenesis, however, in the orthotopic bone model of the critical-sized defects, SDF-1 enhanced calvarial critical-sized bone defect healing similar to VEGF, and PDGF. These results suggest that SDF-1 plays a role in the repair of large critical-sized defect where more cells are needed while not impacting de novo bone formation, which may be associated with the functions of SDF-1 on circulating stem cell recruitment and angiogenesis.
PLoS ONE 05/2014; 9(5):e97035. DOI:10.1371/journal.pone.0097035 · 3.23 Impact Factor
"Multiple studies already indicated apical size as a key factor in pulpal healing and vascularization (Andreasen et al., 1995; Kling et al., 1986). Next to the size of the root apex, the nature of the regenerated tissue is also of major importance, an aspect which is rather ambiguous in current revitalization/cell homing-based regenerative procedures (Huang et al., 2013; Kim et al., 2010; Mullane et al., 2008; Suzuki et al., 2011). However, recent studies indicated the regeneration of organized and vascularized dental tissues after dental stem cell transplantation, even when the size of the apical foramen was limited to 0.7 mm (Iohara et al., 2013; Iohara et al., 2008; Rosa et al., 2013). "
[Show abstract][Hide abstract] ABSTRACT: Within the field of dental tissue engineering, the establishment of adequate tissue vascularization is one of the most important burdens to overcome. As vascular access within the tooth is restricted by the apical foramen, it is of major importance to implement effective vascularization strategies in order to recreate viable components of teeth and periodontal tissues. However, while the current regenerative approaches focus on the use of dental stem cells (DSCs), little is known about these cells and their ability to promote angiogenesis. Therefore, the present study aimed to elucidate the paracrine angiogenic properties of postnatal DSCs, in particular dental pulp stem cells (DPSCs), stem cells from the apical papilla (SCAPs) and dental follicle precursor cells (FSCs). An antibody array, together with RT-PCR and ELISA, pointed out the differential expression of pro-angiogenic as well as anti-angiogenic factors by cultured DSCs and human gingival fibroblasts (HGF-1). Despite the secretion of proliferation-promoting factors, DSCs caused no notable increase in the proliferation of human microvascular endothelial cells (HMEC-1). With regard to other aspects of the angiogenic cascade, DPSCs, SCAPs and HGF-1 significantly promoted endothelial migration in a transwell migration assay. DPSCs also had a pronounced effect on endothelial tubulogenesis, as was shown by an in vitro Matrigel™ assay. In the last part of this study, a chorioallantoic membrane assay demonstrated a sustained pro-angiogenic impact of DPSCs and SCAPs in an in vivo setting. Collectively, these data indicate a predominant pro-angiogenic influence of DPSCs and SCAPS in vitro and in vivo in comparison to FSCs, suggesting that both stem cell populations could potentially promote the vascularization of regenerated dental tissues.
Stem Cell Research 04/2014; 12(3):778-790. DOI:10.1016/j.scr.2014.03.008 · 3.69 Impact Factor
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