Dental stem cells in intraoral regenerative therapy: a systematic review / Células-tronco dentárias na terapia regenerativa intraoral: uma revisão sistemática

Objective: 1) To critically review the published literature on applications of dental stem cells in the regeneration of intraoral tissues. 2) To provide an evidence-based level on research regarding application of dental stem cells in intraoral tissues regeneration. Methodology: This systematic review is conducted as per the JBI guidelines and reported as per the PRISMA. An initial literature search of papers published between 2004 and 2018 yielded 421 manuscripts. Nineteen studies satisfied the inclusion / exclusion criteria and were included for qualitative synthesis. Studies were categorized as animal (11) and human (8) trials. Five independent reviewers critically assessed the included studies. Risk of bias was assessed using SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) bias risk tool, robins-I tool for non-randomised clinical trial and Cochrane Collaboration's Tool for randomised clinical trial. Evidence levels were assessed based on JBI Criteria. Results: Animal trials mainly focused on periodontal regeneration. A high or unclear Risk of bias was more commonly found amongst animal studies. Laboratory, clinical and radiographic evaluation were used to assess the outcome. A total of Eight Human studies were conducted on a total samples size of 153 upon a wide age ranging from seven years to 60 years. Nearly 70% of the human studies used DPSC for regenerating alveolar bone defects. Conclusion: Appropriate well designed double-blind randomized clinical trials of longer duration are yet to be performed. Evidence for the included studies were 1C and 1D as per the JBI Criteria. Stem cell therapy demonstrated promising results in Periodontal tissue and alveolar bone regeneration. However, the number of studies to claim such a benefit are very limited (AU)

Objetivo: 1) Revisar criticamente a literatura publicada sobre aplicações de células-tronco dentárias na regeneração de tecidos intraorais. 2) Fornecer um nível baseado em evidências sobre pesquisas relacionadas à aplicação de células-tronco dentárias na regeneração de tecidos intraorais. Metodologia: Esta revisão sistemática é conduzida de acordo com as diretrizes do JBI e relatada de acordo com o PRISMA. Uma pesquisa bibliográfica inicial de artigos publicados entre 2004 e 2018 resultou em 421 manuscritos. Dezenove estudos satisfizeram os critérios de inclusão / exclusão e foram incluídos para síntese qualitativa. Os estudos foram categorizados como ensaios em animais (11) e humanos (8). Cinco revisores independentes avaliaram criticamente os estudos incluídos. O risco de viés foi avaliado usando a ferramenta de risco de viés do Centro de Revisão Sistemática para Experimentação com Animais de Laboratório (SYRCLE), a ferramenta robins-I para ensaios clínicos não randomizados e a Ferramenta da Colaboração Cochrane para ensaios clínicos randomizados. Os níveis de evidência foram avaliados com base nos critérios JBI. Resultados: Os ensaios em animais focaram principalmente na regeneração periodontal. Um risco alto ou pouco claro de viés foi mais comumente encontrado entre os estudos com animais. Avaliações laboratorial, clínica e radiográfica foram utilizadas para avaliar o resultado. Um total de oito estudos em humanos foram conduzidos em um tamanho total de amostras de 153 com ampla faixa etária, variando de sete a 60 anos. Quase 70% dos estudos em humanos usaram DPSC para regeneração de defeitos ósseos alveolares. Conclusão: Ensaios clínicos randomizados duplo-cegos apropriados e bem elaborados de maior duração ainda precisam ser realizados. As evidências para os estudos incluídos foram 1C e 1D de acordo com os critérios JBI. A terapia com células-tronco demonstrou resultados promissores na regeneração do tecido periodontal e do osso alveolar. No entanto, o número de estudos para reivindicar tal benefício é muito limitado (AU)

Methods of Isolation and Characterization of Stem Cells from Different Regions of Oral Cavity Using Markers: A Systematic Review

BACKGROUND: Periodontitis is a destructive inflammatory disorder of the periodontium caused by the destruction of periodontal tissues namely the PDL, cementum, alveolar bone, and gingiva. Once these tissues are lost, the foremost goal of periodontal therapy is to regenerate the diseased tissues if possible to their original form, architecture, and function. Various regenerative procedures were employed and still a gap was found in achieving the goal. As stem cells are characterized by their ability to self-renew and differentiate to produce specialized cells, there could be a possibility of using them for regenerative therapy. Recently, dental tissues such as the PDL, the dental pulp and the tooth follicle have been recognized as readily available sources of adult stem cells. AIM: The aim was to identify the various sources and methodologies in isolation of stem cells from human oral cavity and its differentiation into various lineages using markers. MATERIALS AND METHODS: The electronic databases PUBMED, GOOGLE SCHOLAR, SCIENCE DIRECT, COCHRANE LIBRARY along with a complimentary manual search of all periodontics journal till the year 2016. Thirteen articles were selected on the basis of the inclusion criteria. Isolation of stem cells from oral cavity through various methods has been evaluated and similarly characterization to different lineages were tabulated as variables of interest. They included human in-vitro and ex-vivo studies. RESULTS: The results showed that PDLSC's and pulpal stem cells are the most common source from where stem cells were isolated. Each source has used different methodology in isolating the stem cells and it was found that STRO-1 was the commonly used marker in all the studies mentioned. CONCLUSIONS: The studies showed that there is no standard protocol existed in isolating the stem cells from different sources of oral cavity. Moreover, there was no standard marker or methodology used in characterization.

Mesenchymal stem cells in the dental tissues: perspectives for tissue regeneration

In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that range from Alzheimer’s disease to cardiac ischemia and regenerative medicine, like bone or tooth loss. Based on their ability to rescue and/or repair injured tissue and partially restore organ function, multiple types of stem/progenitor cells have been speculated. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental tissues are considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that these stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. In dentistry, stem cell biology and tissue engineering are of great interest since may provide an innovative for generation of clinical material and/or tissue regeneration. Mesenchymal stem cells were demonstrated in dental tissues, including dental pulp, periodontal ligament, dental papilla, and dental follicle. These stem cells can be isolated and grown under defined tissue culture conditions, and are potential cells for use in tissue engineering, including, dental tissue, nerves and bone regeneration. More recently, another source of stem cell has been successfully generated from human somatic cells into a pluripotent stage, the induced pluripotent stem cells (iPS cells), allowing creation of patient- and disease-specific stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental stem cell an attractive source of mesenchymal stem cells for tissue regeneration. This review describes new findings in the field of dental stem cell research and on their potential use in the tissue regeneration.

Nos últimos anos, as pesquisas com células tronco têm aumentado exponencialmente devido ao reconhecimento de que seu potencial terapêutico pode melhorar a qualidade de vida de pacientes com diversas doenças, como a doença de Alzheimer, isquemias cardíacas e, até mesmo, nas pesquisas de medicina regenerativa que visa uma possível substituição de órgão perdidos, como por exemplo, os dentes. Baseado em habilidades de reparar tecidos injuriados e restaurar parcialmente as funções de um órgão, diversos tipos de células-tronco têm sido estudadas. Recentes evidências demonstram que as células-tronco são primariamente encontradas em nichos e que certos tecidos apresentam mais células-tronco que outros. Entre estes, os tecidos dentais são considerados como uma fonte rica de células-tronco mesenquimais adequado para aplicações em engenharia tecidual. Sabe-se que estas células têm o potencial de diferenciarem-se em diversos tipos celulares, incluindo osteoblastos, células progenitoras de neurônios, osteoblastos, condrócitos e adipósitos. Na odontologia, a biologia celular e a engenharia tecidual são de grande interesse, pois fornecem inovações na geração de novos materiais clínicos e ou na regeneração tecidual. Estas podem ser isoladas e crescidas em diversos meios de cultura apresentando grande potencial para ser usada na engenharia tecidual, incluindo regeneração de tecidos dentais, nervos e ossos. Recentemente, outra fonte de células tronco tem sido geradas a partir de células somáticas de humanos a um estágio de pluripotência, chamados de células-tronco pluripotente induzida (iPS) levando à criação de células-tronco específicas. Coletivamente, a multipotencialidade, altas taxas de proliferação e acessibilidade, faz das células-tronco dentárias uma fonte atrativa de células-tronco mesenquimais para regeneração tecidual. Esta revisão descreve novos achados no campo da pesquisa com células-tronco dentais e seu potencial uso na regeneração tecidual.