Resorption is the main reason for loss of replanted teeth. The outcome examined in this study is the timing of the onset of resorption. The effect of dichotomised dry and wet time intervals as well as the presence of additional crown damage and of contamination were determined. Of 84 replanted teeth, 67.5% developed resorptions. Twenty-eight had detectable additional crown damage with a more rapid onset being seen in these cases (P=0.009). The critical limit for dry time was 15 min (P=0.038) and significant differences persisted for greater limits also. Serial analysis of the association between the time of onset of root resorption and dichotomised wet time variables failed to yield any significant associations. There was visible contamination detected in 32 teeth and these exhibited a more rapid onset of resorption than the other cases (P=0.030). Teeth with inflammatory root resorption (12.8%) had a more rapid onset of resorption than those that developed replacement resorption (54.7%) (P<0.001). It is concluded that the risk of early resorption is increased in teeth that have additional damage or have contamination, or are kept in dry conditions for longer than 15 min.
A major challenge to the study and treatment of neurogenetic syndromes is accessing live neurons for study from affected individuals. Although several sources of stem cells are currently available, acquiring these involve invasive procedures, may be difficult or expensive to generate and are limited in number. Dental pulp stem cells (DPSC) are multipotent stem cells that reside deep the pulp of shed teeth. To investigate the characteristics of DPSC that make them a valuable resource for translational research, we performed a set of viability, senescence, immortalization and gene expression studies on control DPSC and derived neurons. We investigated the basic transport conditions and maximum passage number for primary DPSC. We immortalized control DPSC using human telomerase reverse transcriptase (hTERT) and evaluated neuronal differentiation potential and global gene expression changes by RNA-seq. We show that neurons from immortalized DPSC share morphological and electrophysiological properties with non-immortalized DPSC. We also show that differentiation of DPSC into neurons significantly alters gene expression for 1305 transcripts. Here we show that these changes in gene expression are concurrent with changes in protein levels of the transcriptional repressor REST/NSRF, which is known to be involved in neuronal differentiation. Immortalization significantly altered the expression of 183 genes after neuronal differentiation, 94 of which also changed during differentiation. Our studies indicate that viable DPSC can be obtained from teeth stored for ≥72hrs, these can then be immortalized and still produce functional neurons for in vitro studies, but that constitutive hTERT immortalization is not be the best approach for long term use of patient derived DPSC for the study of disease.
Dental pulp stem cells (DPSCs) provide an exciting new avenue to study neurogenetic disorders. DPSCs are neural crest-derived cells with the ability to differentiate into numerous tissues including neurons. The therapeutic potential of stem cell-derived lines exposed to culturing ex vivo before reintroduction into patients could be limited if the cultured cells acquired tumorigenic potential. We tested whether DPSCs that spontaneously immortalized in culture acquired features of transformed cells. We analyzed immortalized DPSCs for anchorage-independent growth, genomic instability, and ability to differentiate into neurons. Finally, we tested both spontaneously immortalized and human telomerase reverse transcriptase (hTERT)-immortalized DPSC lines for the ability to form tumors in immunocompromised animals. Although we observed increased colony-forming potential in soft agar for the spontaneously immortalized and hTERT-immortalized DPSC lines relative to lowpassage DPSC, no tumors were detected from any of the DPSC lines tested. We noticed some genomic instability in hTERT-immortalized DPSCs but not in the spontaneously immortalized lines tested. We determined that immortalized DPSC lines generated in our laboratory, whether spontaneously or induced, have not acquired the potential to form tumors in mice. These data suggest cultured DPSC lines that can be differentiated into neurons may be safe for future in vivo therapy for neurobiological diseases. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:905-912 SIGNIFICANCEThis study demonstrated that immortalized dental pulp stem cells (DPSCs) do not form tumors in animals and that immortalized DPSCs can be differentiated into neurons in culture. These results lend support to the use of primary and immortalized DPSCs for future therapeutic approaches to treatment of neurobiological diseases.
Globalization is a broad term referring to the increasing connectivity, integration, and interdependence of economies, societies, technologies, cultures, and political and ecological spheres across the world. This position paper was developed by a working group of the 2007 American Dental Education Association (ADEA) Leadership Institute. The authors explore the effect that globalization has had on dentistry and dental education to date and hypothesize what dental education could look like in the years ahead. While the paper is written from a North American perspective, some of the authors bring international expertise and experience to the topic of global dental education in a flat world. Specific issues and barriers addressed in this position paper include variations in accreditation and licensure requirements in dental education throughout the world; the historical development of dental education models (odontology and stomatology) and the need for congruency of these models in the global environment; the competency-based model of education and its relevance to development and implementation of global dental competencies; and the slow adoption of technological advances in dental education for promoting collaborations and encouraging resource sharing among countries. These challenges are discussed as they affect the implementation of a standardized global dental education that can lead to improved access to oral health care services and better oral and overall health for the citizens of the world.
BackgroundThe inability to analyze gene expression in living neurons from Angelman (AS) and Duplication 15q (Dup15q) syndrome subjects has limited our understanding of these disorders at the molecular level.MethodHere, we use dental pulp stem cells (DPSC) from AS deletion, 15q Duplication, and neurotypical control subjects for whole transcriptome analysis. We identified 20 genes unique to AS neurons, 120 genes unique to 15q duplication, and 3 shared transcripts that were differentially expressed in DPSC neurons vs controls.ResultsCopy number correlated with gene expression for most genes across the 15q11.2-q13.1 critical region. Two thirds of the genes differentially expressed in 15q duplication neurons were downregulated compared to controls including several transcription factors, while in AS differential expression was restricted primarily to the 15q region. Here, we show significant downregulation of the transcription factors FOXO1 and HAND2 in neurons from 15q duplication, but not AS deletion subjects suggesting that disruptions in transcriptional regulation may be a driving factor in the autism phenotype in Dup15q syndrome. Downstream analysis revealed downregulation of the ASD associated genes EHPB2 and RORA, both genes with FOXO1 binding sites. Genes upregulated in either Dup15q cortex or idiopathic ASD cortex both overlapped significantly with the most upregulated genes in Dup15q DPSC-derived neurons.ConclusionsFinding a significant increase in both HERC2 and UBE3A in Dup15q neurons and significant decrease in these two genes in AS deletion neurons may explain differences between AS deletion class and UBE3A specific classes of AS mutation where HERC2 is expressed at normal levels. Also, we identified an enrichment for FOXO1-regulated transcripts in Dup15q neurons including ASD-associated genes EHPB2 and RORA indicating a possible connection between this syndromic form of ASD and idiopathic cases.Electronic supplementary materialThe online version of this article (10.1186/s13229-018-0191-y) contains supplementary material, which is available to authorized users.
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