Genomes and Genes
Mechanisms of dental pulp stem cell differentiation into functional endothelium
Principal Investigator: JACQUES EDUARDO NOR
Abstract: DESCRIPTION (provided by applicant): The Problem: The dental pulp contains pluripotent stem cells that play a critical role in tooth development and tissue regeneration. We have recently demonstrated that human dental pulp stem cels diferentiate into vascular endothelial cells that organize themselves into functional blood vessels in vivo. This exciting observation suggest that dental pulp stem cells can give rise to blood vessels that support the high metabolic demands of "tissue-making", in addition to differentiate into the actual cells that generate the new tissue (e.g. odontoblasts, osteoblasts). However, the mechanisms that control the vasculogenic fate of dental pulp stem cells are not understood. Such knowledge is required to maximize the use of the diferentiation potential of dental pulp stem cells in clinical applications. Hypothesis: In preliminary studies, we demonstrated that vascular endothelial growth factor (VEGF) enhances the vasculogenic potential of dental pulp stem cells. However, the signaling events required for VEGF-induced differentiation of dental pulp stem cells into endothelial cells are unknown. It is known that the Wingless (Wnt) signaling pathway plays a critical role in the determination of cell fate during development. Notably, Wnt inhibits the differentiation of dental pulp stem cells into odontoblasts. But the role of Wnt signaling in directing dental pulp stem cells towards a vasculogenic fate is not understood. Interestingly, a tight correlation between vasculogenesis and bone formation is observed during development. However, the impact of stem cel- mediated vasculogenesis on dentin formation is not known. Here, we will use the tooth as an experimental model for the evaluation of mechanisms that regulate the commitment of stem cells towards the vasculogenic phenotype and determine the role of stem cell-derived blood vessels in mineralized tissue formation. The mechanistic hypothesis of this proposal is: "VEGF and Wnt signaling regulate the vasculogenic fate of dental pulp stem cells". To test this hypothesis, we propose the following specific aims: -Specific Aim #1: To study mechanisms involved in VEGF-induced differentiation of dental pulp stem cells into endothelial cells. -Specific Aim #2: To evaluate the function of Wnt signaling on the determination of dental pulp stem cell fate. -Specific Aim #3: To understand the functional relation between vascular differentiation of dental pulp stem cells and dentinogenesis. Significance: The clinical translation of stem cell-based therapies requires the understanding of mechanisms that control the differentiation fate of these cels. This project aims at the development of mechanism-based approaches that exploit the vasculogenic potential of stem cells to provide the blood vessels required for the generation of new tissues and organs. Our ultimate goal is to employ a deeper understanding of the biology of mesenchymal stem cells of dental origin to benefit patients that require tissue regeneration.
Funding Period: 2011-07-01 - 2015-06-30
more information: NIH RePORT
- Comparative analysis of two colorimetric assays in dental pulp cell densityF Nedel
School of Dentistry Center of Biotechnology, Federal University of Pelotas, Pelotas, RS, Brazil
Int Endod J 44:59-64. 2011..To compare and contrast two colorimetric assays used for the measurement of proliferation using two dental pulp cell types: dental pulp stem cells (DPSC) and human dental pulp fibroblasts (HDPF)...
- Transcriptional factor ATF6 is involved in odontoblastic differentiationJ W Kim
Department of Conservative Dentistry, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, Korea
J Dent Res 93:483-9. 2014..Inhibition of ATF6 decreased ALP activity and mineralization. These results suggest that ER membrane-bound transcriptional factor ATF6 may be involved in odontoblastic differentiation. ..
- Dental pulp tissue engineering in full-length human root canalsV Rosa
Oral Sciences, Faculty of Dentistry, National University of Singapore, Singapore
J Dent Res 92:970-5. 2013....
- Combined effects of simvastatin and enamel matrix derivative on odontoblastic differentiation of human dental pulp cellsLorena Karanxha
Department of Conservative Dentistry, Wonkwang University School of Dentistry, Iksan, Korea
J Endod 39:76-82. 2013..This study further explored the role of extracellular signal-regulated kinase (ERK) as a target and mediator of the differentiation induced by simvastatin in hDPCs...
- Tumor angiogenesis and lymphangiogenesis: tumor/endothelial crosstalk and cellular/microenvironmental signaling mechanismsFausto Gueths Gomes
Nucleus of Cellular and Tecidual Biology NCTBio, Department of Oral Pathology, School of Dentistry, Federal University of Pelotas, Brazil
Life Sci 92:101-7. 2013..Such multifactor studies are critical for the development of future therapeutic approaches for cancer because they take into account the complexities of cellular interactions within the tumor microenvironment...
- Endothelial differentiation of SHED requires MEK1/ERK signalingL W Bento
Angiogenesis Research Laboratory, Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109 1078, USA
J Dent Res 92:51-7. 2013..Collectively, analysis of these data unveiled the VEGF/MEK1/ERK signaling pathway as a key regulator of the endothelial differentiation of dental pulp stem cells...
- Telomeres and tissue engineering: the potential roles of TERT in VEGF-mediated angiogenesisFernando P Hartwig
Biotechnology Unit, Technology Development Center, Federal University of Pelotas, Rio Grande do Sul, Brazil
Stem Cell Rev 8:1275-81. 2012....
- A hydrogel scaffold that maintains viability and supports differentiation of dental pulp stem cellsBruno N Cavalcanti
Department of Cariology, Restorative Sciences, Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI 48109 1078, USA
Dent Mater 29:97-102. 2013..Here, we assessed the compatibility of Puramatrix™ with dental pulp stem cell (DPSC) growth and differentiation...
- Nano-/microfiber scaffold for tissue engineering: physical and biological propertiesBianca Palma Santana
Department of Operative Dentistry School of Dentistry, Federal University of Pelotas, Pelotas, RS, Brazil
J Biomed Mater Res A 100:3051-8. 2012..Therefore, this is a feasible method to produce a scaffold with improved physical characteristics, while at the same time generating an enhanced environment for cell adhesion and proliferation...
- In vitro differentiation and mineralization of dental pulp stem cells on enamel-like fluorapatite surfacesXiaodong Wang
Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, Shaanxi, P R China
Tissue Eng Part C Methods 18:821-30. 2012..This resulted in the differentiation of human DPSCs and mineralized tissue formation, and, thus, demonstrated that it may be a promising biomimetic model for dentin-pulp tissue engineering...
- The stimulation of adipose-derived stem cell differentiation and mineralization by ordered rod-like fluorapatite coatingsJun Liu
Department of Cariology, Restorative Sciences and Endodontics, Dental School, University of Michigan, Ann Arbor, MI 48109, USA
Biomaterials 33:5036-46. 2012..Both the intrinsic properties of the FA crystals and the topography of the FA coating appeared to dominate the cell differentiation and mineralization process...
- Tissue engineering: from research to dental clinicsVinicius Rosa
Post Graduate Program in Dentistry, Dental School, University of Passo Fundo, Passo Fundo, RS, Brazil
Dent Mater 28:341-8. 2012..The objective of this paper is to present the principles underlying tissue engineering and the current scenario, the challenges and the perspectives of this area in Dentistry...
- Regenerative endodontics in light of the stem cell paradigmVinicius Rosa
Department of Cariology, Restorative Sciences and Endodontics, University of Michigan, USA
Int Dent J 61:23-8. 2011..Collectively, these findings suggest new treatment paradigms in the field of endodontics. The goal of this review is to discuss the potential impact of dental pulp stem cells to regenerative endodontics...
- Tooth slice/scaffold model of dental pulp tissue engineeringV T Sakai
Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, 48109 1078, USA
Adv Dent Res 23:325-32. 2011..In addition, we discuss the multipotency of dental pulp stem cells, focusing on the differentiation of these cells into functional odontoblasts and into vascular endothelial cells...
- Dental pulp tissue engineeringFlavio Fernando Demarco
Graduate Program in Dentistry, Federal University of Pelotas, RS, Brazil
Braz Dent J 22:3-13. 2011....
- Functionalized scaffolds to control dental pulp stem cell fateEvandro Piva
Department of Operative Dentistry, School of Dentistry, Federal University of Pelotas, Pelotas, RS, Brazil Department of Cariology, Restorative Sciences, Endodontics, University of Michigan School of Dentistry, Ann Arbor, Michigan
J Endod 40:S33-40. 2014..The long-term goal of this work is to develop stem cell-based therapies that enable the engineering of functional dental pulps capable of generating new tubular dentin in humans. ..
- Stem Cell Based Therapy for Regenerative Endodontics George T J Huang; Fiscal Year: 2013..If successful, a subsequent human trial may be carried out in the future and its success will promise a reduced need of traditional aggressive root canal therapies. ..
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- Non-Thermal Plasma in Biomedicine: A New Paradigm for Redox Cell ActivationGregory Fridman; Fiscal Year: 2013..Results generated from the proposed studies will provide improved methods for tissue repair and regeneration with direct applicability to both clinical research and surgical procedures. ..
- Vasculogenesis and hyperoxia in the developing retina.GERARD ANTHONY LUTTY; Fiscal Year: 2013....
- Multilineage regulation of mesenchymal stem cell differentiation by microRNAsGlyn Palmer; Fiscal Year: 2013..This should improve our current understanding of mesenchymal stem cell differentiation and aid future cell-based therapies for musculoskeletal repair. ..
- Induction of Vascular MorphogenesisLuisa Iruela-Arispe; Fiscal Year: 2013....
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- Center for the Study of Reproductive Biology and Women's HealthJeffrey W Pollard; Fiscal Year: 2013..He holds several senior administrative appointments in the College of Medicine and is well able to administer the proposed SCCPIR internally and to enable effective interactions with other SCCPIRs. ..
- Molecular Regulation of Human Dental Stem Cell PropertiesCun Yu Wang; Fiscal Year: 2013..Moreover, because demethylases, being enzymes, can be readily targeted by small molecule inhibitors, our work may help to develop novel strategies for improving dental and craniofacial tissue regeneration and repair. ..
- Neurohumoral control of veins in hypertensionGregory D Fink; Fiscal Year: 2013..This project tests the idea that altered structure or function of veins also may cause hypertension, and that it may be possible to treat hypertension using drugs that affect veins. ..
- Function and Integration of Stem Cell-derived Cardiac Tissue PatchNenad Bursac; Fiscal Year: 2013..The knowledge obtained in this project will allow us to pursue in the future engineering of a functional cardiac tissue patch made of human stem cells for potential clinical applications. ..
- A Novel Approach for Biomaterials Assisted Regeneration of Pulp-Dentin ComplexSatish Alapati; Fiscal Year: 2013....
- Molecular and Clinical Pharmacology of Retinopathy of PrematurityJacob V Aranda; Fiscal Year: 2013..The NYPD-PRC will surely elevate the level of scientific inquiry on molecular and clinical pharmacology of ROP to hasten its prevention and avert life-long blindness. ..