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1.
J Endod ; 46(9S): S10-S18, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950180

RESUMO

INTRODUCTION: The improvement of regenerative endodontic procedures requires an understanding of the key clinical questions combined with a fundamental biological knowledge of how the dental tissues behave during health, disease, and repair. Therefore, partnerships between clinicians and basic scientists are essential to drive the field forward and improve patient outcomes. METHODS: This review aimed to provide a background to dentin-pulp biology and the interaction between infection, inflammation, and regeneration. RESULTS: We have highlighted how the release of neutrophil extracellular traps (NETs) within the pulp are double-edged; while they aim to limit the bacterial infection, they may actually exacerbate cell death and chronic inflammation. Aberrant levels of these structures may occur because of ineffective host immunologic processes, viral infections, or impaired clearance caused by bacterial virulence factors. We also postulate a proinflammatory link in the pulp between NETs and the inflammasome activated by pathogen-associated molecular patterns and damage-associated molecular patterns. Subsequently, we discuss areas potentially fruitful for future clinical exploitation involving NET inhibitors, inflammasome modulators, phototherapies, and novel epigenetic approaches. CONCLUSIONS: Sustained scientist-clinician research partnerships along with an increased understanding of the association between inflammation and regeneration within the dentin-pulp complex will lead to future patient benefit.


Assuntos
Polpa Dentária , Armadilhas Extracelulares , Dentina , Humanos , Imunidade Inata , Regeneração , Endodontia Regenerativa , Engenharia Tecidual
2.
J Endod ; 46(9S): S105-S114, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950182

RESUMO

INTRODUCTION: Regenerative endodontic therapy (RET) has gained considerable attention and wide approval. Although it is being performed routinely, the outcomes remain unpredictable, and the optimal approaches for treatment are not established. It has been shown that bacterial persistence in root canals in these cases significantly interferes with healing and root maturation. However, few objective clinical studies have evaluated the complex microflora present in the infections or the efficacy of various clinical procedures. In addition, the extent of the infection and biofilm maturation in immature teeth with necrotic pulp has been understudied. Furthermore, most models used in preclinical evaluation of these issues do not fully elucidate the complexity or variability of the clinical situation. RESULTS AND CONCLUSION: In this review, the main biological and clinical problems pertaining to RET will be discussed. Contemporary analysis of complex microbial communities will be reviewed with emphasis on how these types of analyses can provide clinically useful data. In addition, current and proposed approaches for the effective disinfection of the root canal environment without interference with stem cell viability or integrity of the dentin matrix in these cases will be explored. The future of research in this field, including better and more customizable approaches in RET, in light of recent technological advances and progress in endodontics, will be outlined.


Assuntos
Endodontia , Endodontia Regenerativa , Antibacterianos/uso terapêutico , Necrose da Polpa Dentária/tratamento farmacológico , Humanos , Regeneração , Tratamento do Canal Radicular
3.
J Endod ; 46(9S): S128-S134, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950184

RESUMO

Stem cell-mediated regenerative endodontics has reached the human clinical trial phase; however, many issues still exist that prevent such technology to be a widely used clinical practice. These issues are not straightforward and are complicated. They should be because pulp regeneration is dealing with a small dead-end space. In addition, when regeneration is needed, the space is often heavily infected. The true standard of pulp regeneration should be everything except generation of some fibrous connective tissue and amorphous mineral deposit. As of now, we are still far short of reaching the standard of complete vascularized and innervated pulp regeneration with newly formed tubular dentin in all types of teeth. Thus, we need to go back to the bench and use established animal models or create new animal models to tackle those issues. This article will address several key issues including the possibility of pulp regeneration in small canals of molar teeth by enhancing the neovascularization, and whether the organized tubular dentin can be generated on the canal walls. Data from our semi-orthotopic tooth fragment mouse model have shown that complete pulp regeneration using dental pulp stem cells (DPSCs) in small canal has been inconsistent because of limited blood supply. This inconsistency is similar in our orthotopic miniature swine model, although in some cases vascularized pulp-like tissue can be formed throughout the canal space after DPSC transplantation. Furthermore, no tubular dentin was observed in the orthotopic pulp regeneration, despite the fact that DPSCs have the capacity to generate some tubular dentin-like structure in the hydroxyapatite/tricalcium phosphate-mediated ectopic pulp/dentin formation model in mice. Potential strategies to be tested to address these regeneration issues are discussed herein.


Assuntos
Dentina , Regeneração , Animais , Diferenciação Celular , Polpa Dentária , Humanos , Camundongos , Células-Tronco , Suínos , Engenharia Tecidual , Tecidos Suporte
4.
J Endod ; 46(9S): S135-S142, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950185

RESUMO

We showed the safety and efficacy of pulp regenerative therapy by the autologous transplantation of mobilized dental pulp stem cells with granulocyte colony-stimulating factor in a pilot clinical study of young and middle-aged pulpectomized teeth. An experimental study in dogs further demonstrated an age-dependent decline in the amount of regenerated pulp tissue. In our society, in which people will soon live beyond 100 years, this therapy should be efficacious for contributing to the functional survival and endurance of the tooth not only for pulpectomized young teeth but also for aged teeth with periapical disease. However, there are 2 challenges: 1 is enhancing pulp regeneration in aged teeth, and another is complete disinfection before cell transplantation. Thus, this review presents trypsin pretreatment for the former and a novel irrigant, nanobubbles with antibacterial nanopolymers, for the latter, thus demonstrating potential utility for pulp regenerative therapy in aged teeth with periapical disease.


Assuntos
Polpa Dentária , Transplante de Células-Tronco , Envelhecimento , Animais , Cães , Regeneração
5.
J Endod ; 46(9S): S143-S149, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950186

RESUMO

In past years, both cell transplantation and cell homing have been explored for dental pulp tissue engineering. Sufficient evidence shows that after cell transplantation, the regeneration of a functional dentin-pulp complex is possible. A new milestone was reached recently. The concept has now been evaluated in clinical studies. However, the approach is afflicted with high efforts and operating expenses; thus cell homing might be a viable alternative. In this article, the latest developments on the recruitment of resident stem cells by dentin-derived growth factors in injectable fibrin-based scaffold materials will be discussed.


Assuntos
Polpa Dentária , Engenharia Tecidual , Dentina , Regeneração , Células-Tronco , Tecidos Suporte
6.
J Endod ; 46(9S): S161-S174, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950188

RESUMO

INTRODUCTION: A sound and vital pulp is an essential prerequisite for long-term tooth survival and preservation. However, current endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by a synthetic biomaterial. Recently, total or partial pulp regeneration has been proposed as an alternative treatment concept. The aim of this review was to evaluate the current options of pulp treatment and regenerative approaches, both for immature and mature teeth, in a clinical context. METHODS: Clinical success rates of classic treatment options such as pulpotomy or root canal filling after pulpectomy or the removal of necrotic tissue are compared with recent reports on regenerative approaches like revitalization or partial and total pulp regeneration. RESULTS: Revitalization in immature teeth with pulp necrosis is an additional treatment option besides placing an apical plug, leading to clinically acceptable outcomes, although with low predictability regarding the completion of root formation. Coronal regeneration of the amputated pulp in immature teeth constitutes a promising scientific approach, but data from clinical studies are missing. Mature teeth display a reduced potential for regeneration. Regenerative procedures using cell transplantation or cell homing are mainly in the experimental phase with only 2 clinical studies on cell transplantation. In parallel to the further development of regenerative therapies, the classification of pulp diseases should be revised, and the diagnostic tools need improvement. CONCLUSIONS: The rethinking of current concepts for biology-based treatments and improved diagnostic concepts might postpone the point of root canal filling depending on the clinical situation.


Assuntos
Necrose da Polpa Dentária , Tratamento do Canal Radicular , Polpa Dentária , Humanos , Pulpotomia , Regeneração
7.
J Endod ; 46(9S): S19-S25, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950190

RESUMO

INTRODUCTION: The ability to resolve pulpal inflammation to achieve predictable regeneration of the dentin-pulp complex has remained elusive and presents a challenge for clinicians and researchers. Although the dentin-pulp complex can react naturally to injury by forming a bridge of reparative dentin that protects the pulp from further damage, this process is significantly impaired if inflammation persists. Because the secretion of inflammatory cytokines by injured pulpal cells causes significant pain and discomfort to patients, it is critical to resolve pulpal inflammation in a timely manner so as to create a microenvironment conducive for pulpal healing and reparative dentin formation. The emergent field of regenerative endodontics has encouraged the development and application of biologically driven therapies that take advantage of the intrinsic healing capacities of host cells within dental pulp and the periapical complex. METHODS: These studies were designed to test the hypothesis that exposure to hypoxic conditions can modulate the production of inflammatory cytokines/factors by mesenchymal cells in vitro. A multi-domain peptide hydrogel system that is highly conducive for the growth and differentiation of tooth-derived stem cells was used for these studies. Stem cells from human exfoliated deciduous teeth (SHEDs) were first cultured within 3-dimensional hydrogel constructs and then challenged with hypoxic stresses via addition of H2O2. RESULTS: MDP constructs were successfully generated, challenged with H2O2, decellularized and lyophilized, forming a potential biomaterial containing hypoxia induced repair molecules. The ability of cell-derived factors to convert the phenotype of lipopolysaccharide-primed macrophages from a proinflammatory to a pro-resolving state was examined in the presence of the lyophilized SHED cell constructs. CONCLUSIONS: Our data suggest that hypoxia induced SHED cell products can be captured within the hydrogel system and may be useful in the resolution of pulpal inflammation to create a favorable microenvironment for regeneration of the dentin-pulp complex.


Assuntos
Polpa Dentária , Regeneração , Humanos , Peróxido de Hidrogênio , Hipóxia , Inflamação
8.
J Endod ; 46(9S): S42-S45, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950194

RESUMO

AIM: This article seeks to provide a historical perspective on the development of the pulp biology and regeneration research field, especially through the activities of the International Association for Dental Research Pulp Biology and Regeneration research group, and to identify the importance of technological advances for both past and future directions of this research field. RESULTS/DISCUSSION: Key questions needing to be addressed in this field (relating to stem cells, bacterial challenges, progression and control of inflammation, and the specificity of dentinogenic responses during regeneration) to facilitate significant progress are also considered.


Assuntos
Polpa Dentária , Células-Tronco , Regeneração
9.
J Endod ; 46(9S): S46-S55, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950195

RESUMO

Postnatal stem cells critically maintain tissue homeostasis and possess immense potential for tissue regeneration. These stem cells in the orofacial system were not identified until early 2000s when they were first found in the dental pulp and termed dental pulp stem cells (DPSCs). Isolated from either permanent or deciduous teeth, DPSCs were characterized to be highly clonogenic with multidifferentiation and neurovascular properties. Subsequent studies suggested that the origin of DPSCs may be associated with neural crest-derived cells and localized adjacent to neurovascular bundles as indicated by specific surface markers. DPSCs serve as key contributors to pulp homeostasis and injury repair. Mechanistic studies have revealed a fine-tuning regulatory network composed of both extrinsic and intrinsic factors that orchestrate fates of DPSCs. These findings have shaped our understanding of their biological nature as niche responsive progenitors. As we explore the potential of DPSCs in pulp regeneration, preclinical studies have developed diverse DPSC transplantation-based strategies, among which preconditioned DPSCs and DPSC aggregates have shown particular promise. Confirmed by recent clinical advances, DPSC transplantation after pulpectomy has successfully rebuilt the physiological pulp structure in situ functionalized with neurovascularization, indicating a novel regenerative approach for treating pulp diseases. Here, we summarized the 20-year golden journey on DPSCs from the unprecedented discovery to current clinical breakthroughs, while also suggesting future directions and challenges regarding expansion of regenerative applications and evaluation of in vivo DPSCs in diseases and therapies. The historical perspective of this field will provide a blueprint for the stem cell research and enlighten principles for de novo organ regeneration.


Assuntos
Polpa Dentária , Células-Tronco , Diferenciação Celular , Proliferação de Células , Regeneração
10.
J Endod ; 46(9S): S71-S80, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950198

RESUMO

The pulp-dentin complex is innervated by a high density of trigeminal neurons free nerve endings. These neuronal fibers are highly specialized to sense noxious stimuli such as thermal, mechanical, chemical, and biological cues. This robust alert system provides immediate feedback of potential or actual injury triggering reflex responses that protect the teeth from further injury. In the case of patients, pain is the most important experience that leads them to seek oral health care. The adequate removal of the etiology, such as caries, provides ample opportunity for the robust reparative and regenerative potential of the pulp-dentin complex to restore homeostasis. In addition to this elaborated surveillance system, evidence has accumulated that sensory neuronal fibers can potentially modulate various steps of the reparative and regenerative process through cellular communication processes. These include modulation of immunologic, angiogenic, and mineralization responses. Despite these orchestrated cellular events, the defense of the pulp-dentin complex may be overwhelmed, resulting in pulp necrosis and apical periodontitis. Regenerative endodontic procedures have evolved to restore the once lost function of the pulp-dentin complex. After these procedures, a large subset of successful cases demonstrates a positive response to sensitivity testing, suggesting reinnervation of the canal space. This process is likely mediated through cellular and noncellular release of neurotrophic factors such as brain-derived nerve growth factor. In addition, these newly recruited nerve fibers appear equipped to sense thermal stimuli through nonhydrodynamic mechanisms. Collectively, the significance of innervation in the normal physiology of the pulp-dentin complex and its role in regeneration need to be better appreciated to promote further research in this area that could potentially bring new therapeutic opportunities.


Assuntos
Polpa Dentária , Dente , Necrose da Polpa Dentária , Dentina , Humanos , Regeneração , Células Receptoras Sensoriais
11.
J Endod ; 46(9S): S81-S89, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950199

RESUMO

Regenerative dentistry has come a long way from pulp capping to pulp regeneration research, which aims to regenerate the pulp-dentin complex and restore its functions compromised by pulp injury and/or inflammation. Because of unique anatomic limitations of the tooth structure, engineering a suitable microenvironment that facilitates angio/vasculogenesis and innervation is a challenging task. Cell-based tissue engineering approaches have shown great potential in achieving this goal. Biomedical approaches in creating a regenerative microenvironment are mainly represented by either scaffold-based or scaffold-free strategies. The scaffold-based strategy mainly relies on the use of biomaterials to create a structural base that supports cells throughout the process of tissue formation. The scaffold could be a classic 3-dimensional construct with interconnected pores, a hydrogel with cells embedded in it, or a combination of these 2. The scaffold-free approach has been considered a bottom-up strategy that uses cell sheets, spheroids, or tissue strands as building blocks. The outcome of this strategy relies on the capacity of these building blocks to secrete a favorable extracellular matrix and to fuse into larger tissue constructs. Both the scaffold-free and scaffold-based systems are required as complementary, rather than competing, approaches for pulp regeneration. A combined synergetic strategy, through which multicellular building blocks could be integrated with robust 3-dimensional scaffolds, might represent an optimal solution to circumvent some of the major drawbacks of the current methods in pulp regeneration while concurrently fostering their advantages.


Assuntos
Polpa Dentária , Tecidos Suporte , Diferenciação Celular , Regeneração , Engenharia Tecidual
12.
J Endod ; 46(9S): S90-S100, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950200

RESUMO

INTRODUCTION: The dental pulp is highly vascularized and innervated tissue that is uniquely designed, being highly biologically active, while being enclosed within the calcified structure of the tooth. It is well-established that the dental pulp vasculature is a key requirement for the functional performance of the tooth. Therefore, controlled regeneration of the dental pulp vasculature is a challenge that must be met for future regenerative endeavors in endodontics. METHODS: In this perspective review, we address recent progress and challenges on the use of microengineering methods and biomaterials scaffolds to fabricate the dental pulp vascular microenvironment. RESULTS: The conditions required to control the growth and differentiation of vascular capillaries are discussed, together with the conditions required for the formation of mature and stable pericyte-supported microvascular networks in 3-dimensional hydrogels and fabricated microchannels. Recent biofabrication methods, such as 3-dimensional bioprinting and micromolding are also discussed. Moreover, recent advances in the field of organs-on-a-chip are discussed regarding their applicability to dental research and endodontic regeneration. CONCLUSION: Collectively, this short review offers future directions in the field that are presented with the objective of pointing toward successful pathways for successful clinical and translational strategies in regenerative endodontics, with especial emphasis on the dental pulp vasculature.


Assuntos
Polpa Dentária , Dente , Diferenciação Celular , Regeneração , Endodontia Regenerativa , Engenharia Tecidual
13.
Proc Biol Sci ; 287(1935): 20192939, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32933441

RESUMO

Salamanders, frog tadpoles and diverse lizards have the remarkable ability to regenerate tails. Palaeontological data suggest that this capacity is plesiomorphic, yet when the developmental and genetic architecture of tail regeneration arose is poorly understood. Here, we show morphological and molecular hallmarks of tetrapod tail regeneration in the West African lungfish Protopterus annectens, a living representative of the sister group of tetrapods. As in salamanders, lungfish tail regeneration occurs via the formation of a proliferative blastema and restores original structures, including muscle, skeleton and spinal cord. In contrast with lizards and similar to salamanders and frogs, lungfish regenerate spinal cord neurons and reconstitute dorsoventral patterning of the tail. Similar to salamander and frog tadpoles, Shh is required for lungfish tail regeneration. Through RNA-seq analysis of uninjured and regenerating tail blastema, we show that the genetic programme deployed during lungfish tail regeneration maintains extensive overlap with that of tetrapods, with the upregulation of genes and signalling pathways previously implicated in amphibian and lizard tail regeneration. Furthermore, the lungfish tail blastema showed marked upregulation of genes encoding post-transcriptional RNA processing components and transposon-derived genes. Our results show that the developmental processes and genetic programme of tetrapod tail regeneration were present at least near the base of the sarcopterygian clade and establish the lungfish as a valuable research system for regenerative biology.


Assuntos
Peixes/fisiologia , Cauda/fisiologia , Animais , Extremidades/fisiologia , Filogenia , Regeneração/fisiologia
14.
Nat Commun ; 11(1): 4435, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895385

RESUMO

Colonial ascidians are the only chordates able to undergo whole body regeneration (WBR), during which entire new bodies can be regenerated from small fragments of blood vessels. Here, we show that during the early stages of WBR in Botrylloides diegensis, proliferation occurs only in small, blood-borne cells that express integrin-alpha-6 (IA6), pou3 and vasa. WBR cannot proceed when proliferating IA6+ cells are ablated with Mitomycin C, and injection of a single IA6+ Candidate stem cell can rescue WBR after ablation. Lineage tracing using EdU-labeling demonstrates that donor-derived IA6+ Candidate stem cells directly give rise to regenerating tissues. Inhibitors of either Notch or canonical Wnt signaling block WBR and reduce proliferation of IA6+ Candidate stem cells, indicating that these two pathways regulate their activation. In conclusion, we show that IA6+ Candidate stem cells are responsible for whole body regeneration and give rise to regenerating tissues.


Assuntos
Integrina alfa6/metabolismo , Regeneração/fisiologia , Urocordados , Animais , Cordados não Vertebrados/embriologia , Expressão Gênica , Integrina alfa6/genética , Células-Tronco/citologia , Células-Tronco/metabolismo , Urocordados/citologia , Urocordados/embriologia , Urocordados/crescimento & desenvolvimento
16.
Nat Commun ; 11(1): 4549, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917889

RESUMO

Arterial macrophages have different developmental origins, but the association of macrophage ontogeny with their phenotypes and functions in adulthood is still unclear. Here, we combine macrophage fate-mapping analysis with single-cell RNA sequencing to establish their cellular identity during homeostasis, and in response to angiotensin-II (AngII)-induced arterial inflammation. Yolk sac erythro-myeloid progenitors (EMP) contribute substantially to adventitial macrophages and give rise to a defined cluster of resident immune cells with homeostatic functions that is stable in adult mice, but declines in numbers during ageing and is not replenished by bone marrow (BM)-derived macrophages. In response to AngII inflammation, increase in adventitial macrophages is driven by recruitment of BM monocytes, while EMP-derived macrophages proliferate locally and provide a distinct transcriptional response that is linked to tissue regeneration. Our findings thus contribute to the understanding of macrophage heterogeneity, and associate macrophage ontogeny with distinct functions in health and disease.


Assuntos
Artérias/citologia , Arterite/imunologia , Diferenciação Celular/fisiologia , Homeostase/fisiologia , Macrófagos/fisiologia , Envelhecimento/fisiologia , Angiotensina II/administração & dosagem , Angiotensina II/imunologia , Animais , Artérias/fisiologia , Medula Óssea/fisiologia , Transplante de Medula Óssea , Linhagem da Célula , Modelos Animais de Doenças , Feminino , Células-Tronco Hematopoéticas/fisiologia , Humanos , Masculino , Camundongos , Camundongos Transgênicos , RNA-Seq , Regeneração/fisiologia , Análise de Célula Única , Quimeras de Transplante
17.
Nature ; 585(7826): 574-578, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32939089

RESUMO

Epithelial organoids, such as those derived from stem cells of the intestine, have great potential for modelling tissue and disease biology1-4. However, the approaches that are used at present to derive these organoids in three-dimensional matrices5,6 result in stochastically developing tissues with a closed, cystic architecture that restricts lifespan and size, limits experimental manipulation and prohibits homeostasis. Here, by using tissue engineering and the intrinsic self-organization properties of cells, we induce intestinal stem cells to form tube-shaped epithelia with an accessible lumen and a similar spatial arrangement of crypt- and villus-like domains to that in vivo. When connected to an external pumping system, the mini-gut tubes are perfusable; this allows the continuous removal of dead cells to prolong tissue lifespan by several weeks, and also enables the tubes to be colonized with microorganisms for modelling host-microorganism interactions. The mini-intestines include rare, specialized cell types that are seldom found in conventional organoids. They retain key physiological hallmarks of the intestine and have a notable capacity to regenerate. Our concept for extrinsically guiding the self-organization of stem cells into functional organoids-on-a-chip is broadly applicable and will enable the attainment of more physiologically relevant organoid shapes, sizes and functions.


Assuntos
Homeostase , Intestinos/embriologia , Morfogênese , Organoides/embriologia , Tecidos Suporte , Animais , Padronização Corporal , Diferenciação Celular , Linhagem da Célula , Cryptosporidium parvum/patogenicidade , Células-Tronco Embrionárias Humanas/citologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Intestinos/citologia , Intestinos/parasitologia , Intestinos/patologia , Camundongos , Modelos Biológicos , Organoides/citologia , Organoides/parasitologia , Organoides/patologia , Regeneração , Medicina Regenerativa , Células-Tronco , Técnicas de Cultura de Tecidos/métodos , Engenharia Tecidual
19.
Nat Commun ; 11(1): 3866, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737287

RESUMO

Upon severe head injury (HI), blood vessels of the meninges and brain parenchyma are inevitably damaged. While limited vascular regeneration of the injured brain has been studied extensively, our understanding of meningeal vascular regeneration following head injury is quite limited. Here, we identify key pathways governing meningeal vascular regeneration following HI. Rapid and complete vascular regeneration in the meninges is predominantly driven by VEGFR2 signaling. Substantial increase of VEGFR2 is observed in both human patients and mouse models of HI, and endothelial cell-specific deletion of Vegfr2 in the latter inhibits meningeal vascular regeneration. We further identify the facilitating, stabilizing and arresting roles of Tie2, PDGFRß and Dll4 signaling, respectively, in meningeal vascular regeneration. Prolonged inhibition of this angiogenic process following HI compromises immunological and stromal integrity of the injured meninges. These findings establish a molecular framework for meningeal vascular regeneration after HI, and may guide development of wound healing therapeutics.


Assuntos
Traumatismos Craniocerebrais/genética , Células Endoteliais/metabolismo , Neovascularização Fisiológica/genética , Regeneração/genética , Transdução de Sinais/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Circulação Cerebrovascular , Traumatismos Craniocerebrais/metabolismo , Traumatismos Craniocerebrais/patologia , Modelos Animais de Doenças , Células Endoteliais/patologia , Regulação da Expressão Gênica/genética , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , Meninges/lesões , Meninges/metabolismo , Camundongos , Camundongos Knockout , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptor TIE-2/genética , Receptor TIE-2/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/genética
20.
Cell Transplant ; 29: 963689720952089, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32830527

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic, originating from Wuhan, China, is known to cause severe acute respiratory symptoms. The occurrence of a cytokine storm in the lungs is a critical step in the disease pathogenesis, as it causes pathological lesions, pulmonary edema, and acute respiratory distress syndrome, potentially resulting in death. Currently, there is no effective treatment that targets the cytokine storm and helps regenerate the damaged tissue. Mesenchymal stem cells (MSCs) are known to act as anti-inflammatory/immunomodulatory candidates and activate endogenous regeneration. As a result, MSC therapy is a potential treatment approach for COVID-19. Intravenous injection of clinical-grade MSCs into COVID-19 patients can induce an immunomodulatory response along with improved lung function. Dental pulp stem cells (DPSCs) are considered a potential source of MSCs for immunomodulation, tissue regeneration, and clinical application. Although some current clinical trials have treated COVID-19 patients with DPSCs, this therapy has not been approved. Here, we review the potential use of DPSCs and their significance in the development of a therapy for COVID-19.


Assuntos
Infecções por Coronavirus/terapia , Polpa Dentária/citologia , Imunomodulação , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Pneumonia Viral/terapia , Betacoronavirus/imunologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Polpa Dentária/imunologia , Humanos , Imunoterapia/métodos , Inflamação/imunologia , Inflamação/terapia , Pulmão/imunologia , Pulmão/fisiologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/terapia , Células-Tronco Mesenquimais/citologia , Pandemias , Pneumonia Viral/imunologia , Regeneração
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