Venous Blood Derivatives as FBS-Substitutes for Mesenchymal Stem Cells: A Systematic Scoping Review

Abstract Although the biological properties of mesenchymal stem cells (MSC) are well-characterized in vitro, MSC clinical application is still far away to be achieved, mainly due to the need of xenogeneic substances for cell expansion, such as fetal bovine serum (FBS). FBS presents risks regarding pathogens transmissions and internalization of animal's proteins, which can unleash antigenic responses in patients after MSC implantation. A wide range of venous blood derivatives (VBD) has been reported as FBS substitutes showing promising results. Thus, the aim of this study was to conduct a systematic scoping review to analyze whether VBD are effective FBS substitutes for MSC ex vivo expansion. The search was performed in SciVerse ScopusTM, PubMed, Web of ScienceTM, BIREME, Cochrane library up to January 2016. The keywords were selected using MeSH and entry terms. Two independent reviewers scrutinized the records obtained considering specific inclusion criteria. The included studies were evaluated in accordance with a modified Arksey and O' Malley's framework. From 184 found studies, 90 were included. Bone marrow mesenchymal stem cells (BMMSC) were presented in most of these studies. Overall, VBD allowed for either, maintenance of MCS's fibroblast-like morphology, high proliferation, high colony-formation ability and maintenance of multipotency. Besides. MSC expanded in VBD supplements presented higher mitogen activity than FBS. VBD seems to be excellent xeno-free serum for ex vivo expansion of mesenchymal stem cells. However, an accentuated heterogeneity was observed between the carried out protocols for VBD isolation did not allowing for direct comparisons between the included studies.

Resumo Embora as propriedades biológicas das células-tronco mesenquimais (MSC) sejam bem caracterizadas in vitro, a aplicação clínica das MSC ainda está longe de ser alcançada, principalmente devido à necessidade de substâncias xenogênicas para expansão celular, como o soro fetal bovino (FBS). O FBS apresenta riscos quanto às transmissões de patógenos e à internalização de proteínas animais, o que pode desencadear respostas antigênicas em pacientes após a implantação das MSC. Uma vasta gama de derivados do sangue venoso (VBD) têm sido relatada como substitutos do FBS mostrando resultados promissores. Assim, o objetivo deste estudo foi conduzir uma revisão de escopo sistemática para analisar se VBD poderiam ser substitutos do FBS eficazes para expansão das MSC em condições ex vivo. A pesquisa foi realizada no SciVerse Scopus, PubMed, Web of Science, BIREME e biblioteca Cochrane até janeiro de 2016. As palavras-chave foram selecionadas usando MeSH e entre termos. Dois revisores independentes examinaram os registros obtidos considerando critérios de inclusão específicos. Os estudos incluídos foram avaliados de acordo com uma estrutura modificada de Arksey e O 'Malley. Dos 184 estudos encontrados, 90 foram incluídos. As células-tronco da medula óssea (BMMSC) foram utilizadas na maior parte destes estudos. Em geral, o VBD permitiu tanto a manutenção da morfologia semelhante a fibroblastos das MCS, alta proliferação, alta capacidade de formação de colônias e manutenção de multipotêncialidade. Além disso, as MSC expandidas em suplementos derivados do sangue venoso apresentaram uma maior atividade mitogênica do que as expandidas em FBS. Os VBD parecem ser excelentes soro livres de agentes xenogênicos para expansão ex vivo de MSC. Entretanto, observou-se uma heterogeneidade acentuada entre os protocolos realizados para o isolamento VBD, não permitindo assim comparações diretas entre os estudos incluídos.

Células-tronco na saúde e na doença / Stem cells in health and disease

Células-tronco foram recentemente caracterizadas como componentes fundamentais parao desenvolvimento e função de órgãos e tecidos do corpo humano. O descontrole nos processos de diferenciação e sobrevivência das células-tronco tem sido caracterizado como fator etiológico importante em alterações de desenvolvimento do complexo crânio-facial. O conhecimento gerado através de estudos feitos nesta área levantaram a possibilidade de se utilizar células-tronco terapeuticamente para regeneração de tecidos da cavidade oral. Por outro lado, células-tronco também foram caracterizadas em patologias importantes como o câncer. Em câncer, células-tronco participam dos processos de progressão tumoral, bem como na resistência a terapias uma vez que estas células são resistentes a quimioterapia convencional. Tanto em regeneração de tecidos quanto em câncer, é fundamental que se tenha uma compreensão profunda dos mecanismos que governam o comportamento das células-tronco para que se possa desenvolver terapias que sejam seguras e eficazes para os pacientes. O objetivo principal desta revisão é discutir o papel das células tronco em saúde e na doença, usando a regeneração de tecido pulpar e o câncer oral como exemplos de relevância no contexto de Odontologia.

Stem cells were recently characterized as critical components of the development and function of most tissues and organs in humans. Indeed, deregulated survival and differentiation of stem cells have been characterized as important etiological factors of developmental anomalies in the craniofacial region. This knowledge raised the possibility that stem cells could be useful for the therapeutic regeneration of oral tissues. On the other hand, stem cells appear to have an important role in tumor progression, as well as in the resistance of cancer to therapy. This might be due to the fact that stem cells are resilient, long-lived, and tend to survive to conventional chemotherapeutic drugs. Both, in tissue regeneration and in cancer, it is critical to have a profound understanding of the mechanisms that regulate the behavior of stem cells to develop therapies that are safe and effective for patients. The main objective of this review is to discuss the role of stem cells in health and disease, using dental pulp tissue regeneration and oral cancer as examples of relevance to Dentistry.

Dentin bonding: SEM evaluation of the glass ionomer-dentim interface

The purpose of this study was to evaluate the microstructure of the glass ionomerdentin interface after various dentin surface treatments, and to determine which treatment established a hybrid layer at this interface. Thirty sound extracted human teeth (permanent molars) were stored in a disinfectant solution (0.2 percent sodium azide). The occlusal enamel was removed, the dentin exposed and divided into two halves allowing two different dentin treatments in the same tooth. All teeth were mounted in a hydrostatic intrapulpal pressure apparatus, to simulate the in vivo conditions, and removed 12 hours after restorations had been completed. Groups were studied with regards to dentin surface conditioning: 1) no dentin conditioning; 2) GC Conditioner; 3) Vitremer Primer; 4) 35 percent Phosphoric Acid + Vitremer Primer; 5) 35 percent Phosphoric Acid + Scotchbond Multi-Purpose Primer + Scotchbond Multi-Purpose Adhesive Resin. Standard procedures for preparing these specimens for SEM were utilized and the glass ionomer-dentin interface was evaluated under three different magnifications (300, 3000 and 13000 x). The presence and thickness of the hybrid layer was recorded for each specimen and a photomicrograph of a representative area was taken. The results indicated that the interfacial seal was more homogeneous when the dentin was conditioned with 35 percent Phosphoric Acid and either Vitremer Primer or Scotchbond Multi-Purpose was applied prior to the glass ionomer. This suggests that these two dentin treatments may provide better adhesion and less microleakage for glass ionomer restorations.