ArticleNature materials2019
Parenchymal and stromal tissue regeneration of tooth organ by pivotal signals reinstated in decellularized matrix.
Open access · greenAbstract read
In one paragraph
Article in Nature materials, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
9.3field-weighted citation impact, top 1% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Biomolecule-Mediated Therapeutics of the Dentin-Pulp Complex: A Systematic Review.Biomolecules · 2022Pooled it
- Mechanically sensitized hydrogel microspheres trigger membrane receptor switch for cartilage repair.Bioactive materials · 2026Article
- The Effect of miR-129-5p on the Proliferation and Osteogenic Differentiation of Human Dental Pulp Stem Cells.International dental journal · 2026Article
- Foxq1-Wnt5a Axis Activation in Dental Papilla Stem Cells Promotes Odontogenesis on Acellular Matrix: A Laboratory Investigation.International endodontic journal · 2026Article
- Decellularized Dental Pulp Matrix Hydrogel Promotes Functional Endodontic Regeneration In Situ.International endodontic journal · 2026Article
- Fuel to fire: developmental niche-empowered ApoEVs unlock adult hierarchical tissue regenerative potential via mitochondrial complex I-driven developmental metabolic profile.International journal of oral science · 2026Article
- GREM1 acts in leptin receptor-expressing skeletal cells to mediate peri-implant fibrosis.Nature communications · 2026Article
- Wnt3a promotes in situ dentin formation through NKD1-MSX1 axis-mediated odontogenic differentiation of dental pulp stem cells.International journal of oral science · 2026Article
- Odontogenic exosomes simulating the developmental microenvironment promote complete regeneration of pulp-dentin complex in vivo.Journal of advanced research · 2025Article
- The comprehensive progress of tooth regeneration from the tooth development to tissue engineering and clinical application.Cell regeneration (London, England) · 2025Review
- Cancer-associated fibroblasts promote growth and dissemination of esophageal squamous cell carcinoma cells by secreting WNT family member 5A.Molecular and cellular biochemistry · 2025Article
- Regenerative endodontic therapy: From laboratory bench to clinical practice.Journal of advanced research · 2025Review
- Mandible-derived extracellular vesicles regulate early tooth development in miniature swine via targeting KDM2B.International journal of oral science · 2025Article
- Review
- Research progress of dental pulp regeneration treatment.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Review
- TSG-6 Inhibits the NF-κB Signaling Pathway and Promotes the Odontogenic Differentiation of Dental Pulp Stem Cells via CD44 in an Inflammatory Environment.Biomolecules · 2024Article
- X-Ray Visible Protein Scaffolds by Bulk Iodination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Research progress of biomimetic materials in oral medicine.Journal of biological engineering · 2023Review
- Article
- High-Throughput Bioprinting of Geometrically-Controlled Pre-Vascularized Injectable Microgels for Accelerated Tissue Regeneration.Advanced healthcare materials · 2023Article
Corrections and comments
- Commented on byA pulpy story.2019
Authors and funding
48 authors at 12 institutions in 2 countries.
Ling HeColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.ORCID http://orcid.org/0000-0002-8692-7530
Jian ZhouColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Mo ChenColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Chyuan-Sheng LinDepartment of Pathology and Cell Biology, Columbia University, New York, NY, USA.
Sahng G KimColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Yue ZhouColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Lusai XiangColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Ming XieColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Hanying BaiColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Hai YaoDepartment of Bioengineering, Clemson University, Charleston, SC, USA.
Changcheng ShiDepartment of Bioengineering, Clemson University, Charleston, SC, USA.
Paulo G CoelhoDepartment of Biomaterials and Biomimetics, New York University, New York, NY, USA.
Timothy G BromageDepartment of Biomaterials and Biomimetics, New York University, New York, NY, USA.ORCID http://orcid.org/0000-0002-9843-7993
Bin HuDepartment of Biomaterials and Biomimetics, New York University, New York, NY, USA.
Nick TovarDepartment of Biomaterials and Biomimetics, New York University, New York, NY, USA.
Lukasz WitekDepartment of Biomaterials and Biomimetics, New York University, New York, NY, USA.
Jiaqian WuVivian L. Smith Department of Neurosurgery, Center for Stem Cell and Regenerative Medicine University of Texas McGovern Medical School at Houston, Houston, TX, USA.
Kenian ChenVivian L. Smith Department of Neurosurgery, Center for Stem Cell and Regenerative Medicine University of Texas McGovern Medical School at Houston, Houston, TX, USA.
Wei GuDepartment of Pathology and Cell Biology, Columbia University, New York, NY, USA.
Jinxuan ZhengColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Tzong-Jen SheuUniversity of Rochester Medical Center, School of Medicine and Dentistry, Rochester, NY, USA.
Juan ZhongColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Jin WenColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Yuting NiuColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Bin ChengColumbia University Mailman School of Public Health, Department of Biostatistics, New York, NY, USA.
Qimei GongColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
David M OwensDepartment of Pathology and Cell Biology, Columbia University, New York, NY, USA.
Milda StanislauskasDepartment of Dermatology, Columbia University, New York, NY, USA.
Jasmine PeiColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Gregory ChotkowskiPrivate Practice, New York, NY, USA.
Sainan WangColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Guodong YangColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
David J ZegarelliColumbia University College of Dental Medicine, New York, NY, USA.
Xin ShiColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Myron FinkelPrivate Practice, New York, NY, USA.
Wen ZhangColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Junyuan LiColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.
Jiayi ChengColumbia University, Center for Craniofacial Regeneration, New York, NY, USA.ORCID http://orcid.org/0000-0002-4262-9136
Dennis P TarnowColumbia University College of Dental Medicine, New York, NY, USA.
Xuedong ZhouState Key Laboratory of Oral Diseases, West China Hospital of Stomatology, West China School of Stomatology, Sichuan University, Chengdu, China.
Zuolin WangDepartment of Conservative Dentistry, Laboratory of Biomedical Science and Translational Medicine, School of Stomatology, Tongji University, Shanghai, China.
Xinquan JiangDepartment of Prosthodontics, Shanghai Jiao Tong University, Shanghai, China.
Alexander RomanovInstitute of Comparative Medicine, Columbia University Medical Center, New York, NY, USA.
David W RoweCenter for Regenerative Medicine and Skeletal Development, University of Connecticut Health Science Center, Farmington, CT, USA.
Songlin WangMolecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
Ling YeState Key Laboratory of Oral Diseases, West China Hospital of Stomatology, West China School of Stomatology, Sichuan University, Chengdu, China.
Junqi LingOperative Dentistry and Endodontics, Guanghua School of Stomatology, Affiliated Stomatology Hospital, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China. lingjunqi@163.com.
Jeremy MaoColumbia University, Center for Craniofacial Regeneration, New York, NY, USA. jmao@columbia.edu.ORCID http://orcid.org/0000-0003-0776-0689
Columbia University · USSun Yat-sen University · CNNew York University · USCapital Medical University · CNShanghai Jiao Tong University · CNClemson University · USSichuan University · CNThe University of Texas Health Science Center at Houston · USTongji University · CNColumbia University Irving Medical Center · USUConn Health · USUniversity of Rochester Medical Center · US
Funding
Tissue Structural and Neural Remodeling in Human Sacroiliac JointP20GM121342 · NIGMS · CLEMSON UNIVERSITY · PI Hai Yao · 2018 to 2026
$24.7MT-COHR: Training in Craniofacial and Oral Health ResearchT32DE017551 · NIDCR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI YAO, HAI · 2006 to 2025
$10.3MMeniscus Regeneration by Endogenous Stem/Progenitor CellsR01AR065023 · NIAMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FORTIER, LISA A, LEE, CHANG HUN · 2014 to 2018
$4.6MTranslational and Precision Medicine Resources Core (TRAP)P30AR069632 · NIAMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CHRISTIANO, ANGELA M · 2016 to 2020
$3.9MPre-clinical Models of Odontic Analogs by Endogenous Stem CellsR01DE023112 · NIDCR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAO, JEREMY J · 2013 to 2016
$2.9MSkeletal Phenotyping of Heterozygotes from IMPC Embryonic Lethal LinesR01HD098636 · NICHD · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI MAYE, PETER, ROWE, DAVID W. · 2019 to 2023
$2.8MContinuous root formation in developing teeth by molecular cuesR01DE025643 · NIDCR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI EMBREE, MILDRED CHRISTINE, LEE, CHANG HUN · 2016 to 2018
$2.1MAdult Stem Cells: Osteoblast Differentiation and EngraftmentR01AR052374 · NIAMS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI ROWE, DAVID W. · 2007 to 2011
$1.5MNIAMS NIH HHS P30 AR069632NIAMS NIH HHS R01 AR052374NIAMS NIH HHS R01 AR065023NICHD NIH HHS R01 HD098636NIDCR NIH HHS R01 DE023112NIDCR NIH HHS R01 DE025643NIDCR NIH HHS R01 DE026297NIDCR NIH HHS T32 DE017551NIGMS NIH HHS P20 GM121342
Abstract
Cells are transplanted to regenerate an organs' parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite the common use of a decellularized matrix, little is known as to the pivotal signals that must be restored for tissue or organ regeneration. We report that Alx3, a developmentally important gene, orchestrated adult parenchymal and stromal regeneration by directly transactivating Wnt3a and vascular endothelial growth factor. In contrast to the modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma that involved vascular endothelial growth factor signalling, but also parenchymal dentin via the Wnt/β-catenin pathway. In an orthotopic large-animal model following parenchyma and stroma ablation, Wnt3a-recruited endogenous cells regenerated neurovascular stroma and differentiated into parenchymal odontoblast-like cells that extended the processes into newly formed dentin with a structure-mechanical equivalency to native dentin. Thus, the Alx3-Wnt3a axis enables postnatal progenitors with a modest innate regenerative capacity to regenerate adult tissues. Depleted signals in the decellularized matrix may be reinstated by a developmentally pivotal gene or corresponding protein.
Indexed as
AdolescentAnimalsFemaleHomeodomain ProteinsHumansIncisorMice, Inbred StrainsMolar, ThirdOrgan Culture TechniquesParenchymal TissuePregnancyPromoter Regions, GeneticRegenerationStromal CellsSwineToothAlx3 protein, mouseHomeodomain ProteinsVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouseWnt3A ProteinWNT3A protein, humanWnt3a protein, mouse
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