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Research Overview

Periodontal Tissue Regeneration. Stem cells are a population of cells capable of providing replacement cells for a given differentiated cell type (Blau et al. 2001). In our lab we are applying stem cell-based technologies to generate novel tissue-engineered, smart periodontal implants that use biomimetic strategies with the ultimate goal of achieving full regeneration of lost periodontal tissues. Mesenchymal periodontal tissues such as cementum, alveolar bone, and periodontal ligament are neural crest-derived entities that emerge from the dental follicle at the onset of root formation (Diekwisch 2001, 2002). In order to mimic the differentiation of periodontal cells from undifferentiated progenitors we have deciphered, recapitulated or mimicked the molecular and cellular events that occur during periodontal tissue differentiation in the developing periodontium (Luan et al. 2009, Dangaria et al. 2009). Recently, we have succeeded in regenerating the periodontium of a molar tooth root using apatite surface topography and periodontal progenitor cells (Dangaria et al. 2010).

Building a Tooth. From 2006 – 2007, we contributed to an NIDCR planning grant P20 DE17447 “The Chicago Blueprint for Dental Regeneration” and a UIC 2010 Interdisciplinary Seed Grant. The focus of this research was to generate a biological tooth substitute. Aspects of this research endeavor include biological regeneration of dentin, enamel, and periodontal tissues. The ultimate goal was to generate biological tooth replacements for diseased and lost teeth using scaffolding, nanotechnology, genomics, proteomics, and stem cell technology. Most recently, together with Dr. Sarah Millar at the University of Pennsylvania, we have collaborated on the role of ß-catenin in tooth neogenesis (Liu et al. 2010).

Periodontal Regeneration. Gum disease is a serious infection of the periodontal tissues that eventually leads to tooth loss. About 80 percent of U.S. adults suffer from gum disease, according to the National Institute of Dental and Craniofacial Research. Recently, we have developed and successfully tested a new technique to anchor teeth back in the jaws by applying a stem cell-based approach. Mouse molar periodontal progenitor cells were expanded and then seeded on barren rat molars. The stem cell-treated molars were reinserted into the tooth sockets of rats. After two and four months, the stem cells aligned and formed new fibrous attachments between the tooth and bone, firmly attaching the replanted tooth into the animal's mouth. Tissue sections showed that the replanted tooth was surrounded by newly formed, functional periodontal ligament fibers and new cementum, the essential ingredients of a healthy tooth attachment. In contrast, tooth molars that were replanted without new stem/progenitor cells were either lost or loosely attached and were resorbed. To verify that the ligament was formed by the transplanted stem cells and not by the animal's own cells, stem cells were labeled with green fluorescent protein prior to seeding them on the molars and re-inserting the teeth into the animal’s mouth. The success of our procedure was based on a combination of natural tooth root surface structure together with periodontal progenitor cells. This strategy could be used for replanting teeth that were lost due to trauma or as a novel approach for tooth replacement using tooth-shaped replicas. The periodontal progenitors used in the present study were characterized in a study published in the journal Stem Cells and Development (Dangaria et al. in press) and the replantation technique was published in the journal Tissue Engineering (Dangaria et al. in press). Studies were based on previous findings on periodontal progenitors and extracellular matrices from our lab (Luan et al. 2006, Luan et al. 2009, Dangaria et al. 2009).

Musical chairs. The three principle investigators involved in NIDCR Building a Tooth planning process were Richard Maas (Harvard University), Tom Diekwisch (UIC), and Malcolm Snead (University of Southern California). Note the significant change in position as the investigators moved from summit to summit.

Dangaria, S., Ito, Y., Yin, L.L., Valdrè, G., Luan, X., and Diekwisch, T.G.H. (2010). Apatite microtopographies instruct signaling tapestries for progenitor-driven new attachment of teeth. Tissue Engineering A. Pub Med ID: 20795795.

Dangaria, S., Ito, Y., Luan, X., and Diekwisch, T.G.H. (2010). Differentiation of neural crest-derived intermediate pluripotent progenitors into committed periodontal populations involves unique molecular signature changes, cohort shifts, and epigenetic modifications. Stem Cells and Development. Pub Med ID: 20665818.

Liu F., Dangaria, S., Andl, T., Zhang, Y., Wright, A.C., Damek-Poprava, M., Piccolo, S., Nagy, A., Taketo, M.M., Diekwisch, T.G.H., Akintoye, S.O., Millar, S.E. (2010). ß-catenin initiates tooth neogenesis from adult rodent incisor. J. Dent. Res. 89, 909-914.

Jin, T., Ito, Y., Luan, X., Dangaria, S., Walker, C., Allen, M., Kulkarni A., Gibson, C., Braatz, R., Liao, X., and Diekwisch, T.G.H. (2009). Supramolecular compaction through polyproline motif elongation as a mechanism for vertebrate enamel evolution. PLoS Biology 7(12): e1000262. doi:10.1371/journal.pbio.1000262.

Luan, X., Dangaria, S., Ito, Y., Walker, C., Jin, T., Schmidt, M., Galang, T., and Druzinsky, R. (2009). Neural crest lineage segregation: a blueprint for periodontal regeneration. Journal of Dental Research 88, 781-791.

Dangaria, S.J., Ito, Y., Walker, C., Druzinsky, R., Luan, X., and Diekwisch, T.G.H. (2009). Extracellular matrix-mediated differentiation of periodontal progenitor cells. Differentiation 78, 79-90.

Luan, X., Ito, Y., Dangaria, S., and Diekwisch, T.G.H. (2006). Dental follicle progenitor cell heterogeneity in the developing mouse periodontium. Stem Cells and Development 15, 595-608.

Diekwisch, T.G.H. (2006). When genomes and stem cells meet: New perspectives for medical applications of stem cell research through the Australian/U.S. collaborative. Stem Cells Dev. 15, 475-477.

Fukui, T., Akutsu, S., Hirashita, A., Oida, S., Diekwisch, T.G.H., and Yamane, A. (2004). Effects of exogenous bone morphogenetic protein 2 on the formation of mouse molar tooth germ. J. Oral Biosci. 46, 530-535.