RESUMEN

The dental pulp is the only soft tissue structure within the tooth, serving functions such as sensation and nutrition. However, the dental pulp is highly susceptible to necrosis due to external factors. Currently, root canal therapy is the most commonly used treatment for pulp necrosis. Nevertheless, teeth treated with root canal therapy are prone to secondary infections and adverse outcomes like vertical root fractures. Regenerative endodontic therapy has emerged as a solution, aiming to replace damaged tooth structures, including dentin, root structure, and the pulp-dentin complex cells. This approach demonstrates significant advantages in addressing clinical symptoms and achieving regeneration of the root and even the pulp. Since the discovery of dental pulp stem cells, regenerative endodontic therapy has gained new momentum. Advances in cell transplantation and cell homing techniques have rapidly developed, showing promising potential for clinical applications.

Asunto(s)

Pulpa Dental , Regeneración , Trasplante de Células Madre , Pulpa Dental/fisiología , Pulpa Dental/citología , Humanos , Regeneración/fisiología , Trasplante de Células Madre/métodos , Endodoncia Regenerativa/métodos , Células Madre/citología , Tratamiento del Conducto Radicular/métodos , Ingeniería de Tejidos/métodos , Necrosis de la Pulpa Dental/terapia

RESUMEN

Endogenous stem cell homing refers to the transport of endogenous mesenchymal stem cells (MSCs) to damaged tissue. The paradigm of using well-designed biomaterials to induce resident stem cells to home in to the injured site while coordinating their behavior and function to promote tissue regeneration is known as endogenous regenerative medicine (ERM). ERM is a promising new avenue in regenerative therapy research, and it involves the mobilizing of endogenous stem cells for homing as the principal means through which to achieve it. Comprehending how mesenchymal stem cells home in and grasp the influencing factors of mesenchymal stem cell homing is essential for the understanding and design of tissue engineering. This review summarizes the process of MSC homing, the factors influencing the homing process, analyses endogenous stem cell homing studies of interest in the field of skin tissue repair, explores the integration of endogenous homing promotion strategies with cellular therapies and details tissue engineering strategies that can be used to modulate endogenous homing of stem cells. In addition to providing more systematic theories and ideas for improved materials for endogenous tissue repair, this review provides new perspectives to explore the complex process of tissue remodeling to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.

Asunto(s)

Materiales Biocompatibles , Células Madre Mesenquimatosas , Ingeniería de Tejidos , Cicatrización de Heridas , Humanos , Células Madre Mesenquimatosas/citología , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/fisiología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ingeniería de Tejidos/métodos , Animales , Medicina Regenerativa/métodos , Andamios del Tejido/química , Movimiento Celular/efectos de los fármacos , Piel , Trasplante de Células Madre Mesenquimatosas/métodos

RESUMEN

In recent years, cell therapy has provided desirable properties for promising new drugs. Mesenchymal stem cells are promising candidates for developing genetic engineering and drug delivery strategies due to their inherent properties, including immune regulation, homing ability and tumor tropism. The therapeutic potential of mesenchymal stem cells is being investigated for cancer therapy, inflammatory and fibrotic diseases, among others. Mesenchymal stem cells are attractive cellular carriers for synthetic nanoparticles for drug delivery due to their inherent homing ability. In this review, we comprehensively discuss the various genetic and non-genetic strategies of mesenchymal stem cells and their derivatives in drug delivery, tumor therapy, immune regulation, tissue regeneration and other fields. In addition, we discuss the current limitations of stem cell therapy and the challenges in clinical translation, aiming to identify important development areas and potential future directions.

Asunto(s)

Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Humanos , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/inmunología , Animales , Sistemas de Liberación de Medicamentos , Neoplasias/terapia , Neoplasias/inmunología

RESUMEN

NADPH oxidase 2 (Nox2), a superoxide-generating enzyme, is a source of reactive oxygen species (ROS) that regulate the intracellular redox state, self-renewal, and fate of hematopoietic stem/progenitor cells (HSPCs). Nox2 complex expressed on HSPCs associated with several activated cell membrane receptors increases the intracellular level of ROS. In addition, ROS are also released from mitochondria and, all together, are potent activators of intracellular pattern recognition receptor Nlrp3 inflammasome, which regulates the trafficking, proliferation, and metabolism of HSPCs. In the current study, we noticed that Nox2-deficient mice, despite the increased number of HSPCs in the bone marrow (BM), show hematopoietic defects illustrated by delayed recovery of peripheral blood (PB) hematopoietic parameters after sublethal irradiation and mobilize fewer HSPCs after administration of G-CSF and AMD3100. Moreover, Nox2-deficient HSPCs engraft poorly after transplantation into normal syngeneic recipients. To explain these defects at the molecular level, we hypothesized that Nox2-KO decreased ROS level does not efficiently activate Nlrp3 inflammasome, which plays a crucial role in regulating the trafficking of HSPCs. Herein, we report Nox2-deficient HSPCs display i) defective migration to major chemoattractant, ii) impaired intracellular activation of Nlrp3 inflammasome, and iii) a defect in membrane lipid raft (MLRs) formation that is required for a proper chemotactic response to pro-migratory factors. We conclude that Nox2-derived ROS enhances in Nlrp3 inflammasome-dependent manner HSPCs trafficking by facilitating MLRs assemble on the outer cell membranes, and defect in Nox2 expression results in impaired activation of Nlrp3 inflammasome, which affects HSPCs migration.

RESUMEN

BACKGROUND: Osteoarthritis (OA) is an aging-related degenerative joint disorder marked by joint discomfort and rigidity. Senescent chondrocytes release pro-inflammatory cytokines and extracellular matrix-degrading proteins, creating an inflammatory microenvironment that hinders chondrogenesis and accelerates matrix degradation. Targeting of senescent chondrocytes may be a promising approach for the treatment of OA. Herein, we describe the engineering of an injectable peptide-hydrogel conjugating a stem cell-homing peptide PFSSTKT for carrying plasmid DNA-laden nanoparticles and Tanshinon IIA (pPNP + TIIA@PFS) that was designed to attenuate OA progression by improving the senescent microenvironment and fostering cartilage regeneration. RESULTS: Specifically, pPNP + TIIA@PFS elevates the concentration of the anti-aging protein Klotho and blocks the transmission of senescence signals to adjacent healthy chondrocytes, significantly mitigating chondrocyte senescence and enhancing cartilage integrity. Additionally, pPNP + TIIA@PFS recruit bone mesenchymal stem cells and directs their subsequent differentiation into chondrocytes, achieving satisfactory chondrogenesis. In surgically induced OA model rats, the application of pPNP + TIIA@PFS results in reduced osteophyte formation and attenuation of articular cartilage degeneration. CONCLUSIONS: Overall, this study introduces a novel approach for the alleviation of OA progression, offering a foundation for potential clinical translation in OA therapy.

Asunto(s)

Condrocitos , Condrogénesis , Glucuronidasa , Hidrogeles , Proteínas Klotho , Células Madre Mesenquimatosas , Osteoartritis , Plásmidos , Ratas Sprague-Dawley , Animales , Osteoartritis/terapia , Osteoartritis/tratamiento farmacológico , Hidrogeles/química , Ratas , Condrocitos/metabolismo , Condrocitos/efectos de los fármacos , Glucuronidasa/metabolismo , Glucuronidasa/farmacología , Condrogénesis/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Masculino , Cartílago Articular/efectos de los fármacos , Cartílago Articular/metabolismo , Progresión de la Enfermedad , Nanopartículas/química , Humanos , ADN , Senescencia Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos

RESUMEN

Studying cell settlement in the three-dimensional structure of synthetic biomaterials over time is of great interest in research and clinical translation for the development of artificial tissues and organs. Tracking cells as physical objects improves our understanding of the processes of migration, homing, and cell division during colonisation of the artificial environment. In this study, the 3D environment had a direct effect on the behaviour of biological objects. Recently, deep learning-based algorithms have shown significant benefits for cell segmentation tasks and, furthermore, for biomaterial design optimisation. We analysed the primary LHON fibroblasts in an artificial 3D environment after adeno-associated virus transduction. Application of these tools to model cell homing in biomaterials and to monitor cell morphology, migration and proliferation indirectly demonstrated restoration of the normal cell phenotype after gene manipulation by AAV transduction. Following the 3Rs principles of reducing the use of living organisms in research, modeling the formation of tissues and organs by reconstructing the behaviour of different cell types on artificial materials facilitates drug testing, the study of inherited and inflammatory diseases, and wound healing. These studies on the composition and algorithms for creating biomaterials to model the formation of cell layers were inspired by the principles of biomimicry.

RESUMEN

Microorganisms, physical factors such as temperature or mechanical injury, and chemical factors such as free monomers from composite resin are the main causes of dental pulp diseases. Current clinical treatment methods for pulp diseases include the root canal therapy, vital pulp therapy and regenerative endodontic therapy. Regenerative endodontic therapy serves the purpose of inducing the regeneration of new functional pulp tissues through autologous revascularization or pulp tissue engineering. This article first discusses the current clinical methods and reviews strategies as well as the research outcomes regarding the pulp regeneration. Then the in vivo models, the prospects and challenges for regenerative endodontic therapy were further discussed.

RESUMEN

PURPOSE: This study aimed to evaluate the potential of astragalus polysaccharide (APS) pretreatment in enhancing the homing and anti-peritoneal fibrosis capabilities of bone marrow mesenchymal stromal cells (BMSCs) and to elucidate the underlying mechanisms. METHODS: Forty male Sprague-Dawley rats were allocated into four groups: control, peritoneal dialysis fluid (PDF), PDF + BMSCs, and PDF + APSBMSCs (APS-pre-treated BMSCs). A peritoneal fibrosis model was induced using PDF. Dil-labeled BMSCs were administered intravenously. Post-transplantation, BMSC homing to the peritoneum and pathological alterations were assessed. Stromal cell-derived factor-1 (SDF-1) levels were quantified via enzyme-linked immunosorbent assay (ELISA), while CXCR4 expression in BMSCs was determined using PCR and immunofluorescence. Additionally, a co-culture system involving BMSCs and peritoneal mesothelial cells (PMCs) was established using a Transwell setup to examine the in vitro effects of APS on BMSC migration and therapeutic efficacy, with the CXCR4 inhibitor AMD3100 deployed to dissect the role of the SDF-1/CXCR4 axis and its downstream impacts. RESULTS: In vivo and in vitro experiments confirmed that APS pre-treatment notably facilitated the targeted homing of BMSCs to the peritoneal tissue of PDF-treated rats, thereby amplifying their therapeutic impact. PDF exposure markedly increased SDF-1 levels in peritoneal and serum samples, which encouraged the migration of CXCR4-positive BMSCs. Inhibition of the SDF-1/CXCR4 axis through AMD3100 application diminished BMSC migration, consequently attenuating their therapeutic response to peritoneal mesenchyme-to-mesothelial transition (MMT). Furthermore, APS upregulated CXCR4 expression in BMSCs, intensified the activation of the SDF-1/CXCR4 axis's downstream pathways, and partially reversed the AMD3100-induced effects. CONCLUSION: APS augments the SDF-1/CXCR4 axis's downstream pathway activation by increasing CXCR4 expression in BMSCs. This action bolsters the targeted homing of BMSCs to the peritoneal tissue and amplifies their suppressive influence on MMT, thereby improving peritoneal fibrosis.

Asunto(s)

Planta del Astrágalo , Quimiocina CXCL12 , Células Madre Mesenquimatosas , Fibrosis Peritoneal , Polisacáridos , Ratas Sprague-Dawley , Receptores CXCR4 , Animales , Receptores CXCR4/metabolismo , Quimiocina CXCL12/metabolismo , Ratas , Masculino , Fibrosis Peritoneal/tratamiento farmacológico , Fibrosis Peritoneal/metabolismo , Polisacáridos/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Modelos Animales de Enfermedad , Ciclamas/farmacología

RESUMEN

This study investigated the incorporation of sources of calcium, phosphate, or both into electrospun scaffolds and evaluated their bioactivity on human dental pulp cells (HDPCs). Additionally, scaffolds incorporated with calcium hydroxide (CH) were characterized for degradation, calcium release, and odontogenic differentiation by HDPCs. Polycaprolactone (PCL) was electrospun with or without 0.5% w/v of calcium hydroxide (PCL + CH), nano-hydroxyapatite (PCL + nHA), or ß-glycerophosphate (PCL + ßGP). SEM/EDS analysis confirmed fibrillar morphology and particle incorporation. HDPCs were cultured on the scaffolds to assess cell viability, adhesion, spreading, and mineralized matrix formation. PCL + CH was also evaluated for gene expression of odontogenic markers (RT-qPCR). Data were submitted to ANOVA and Student's t-test (α = 5%). Added CH increased fiber diameter and interfibrillar spacing, whereas ßGP decreased both. PCL + CH and PCL + nHA improved HDPC viability, adhesion, and proliferation. Mineralization was increased eightfold with PCL + CH. Scaffolds containing CH gradually degraded over six months, with calcium release within the first 140 days. CH incorporation upregulated DSPP and DMP1 expression after 7 and 14 days. In conclusion, CH- and nHA-laden PCL fiber scaffolds were cytocompatible and promoted HDPC adhesion, proliferation, and mineralized matrix deposition. PCL + CH scaffolds exhibit a slow degradation profile, providing sustained calcium release and stimulating HDPCs to upregulate odontogenesis marker genes.

RESUMEN

Articular cartilage defect is challenged by insufficient regenerative ability of cartilage. Catalpol (CA), the primary active component of Rehmanniae Radix, could exert protective effects against various diseases. However, the impact of CA on the treatment of articular cartilage injuries is still unclear. In this study, full-thickness articular cartilage defect was induced in a mouse model via surgery. The animals were intraperitoneally injected with CA for 4 or 8 weeks. According to the results of macroscopic observation, micro-computed tomography CT (µCT), histological and immunohistochemistry staining, CA treatment could promote mouse cartilage repair, resulting in cartilage regeneration, bone structure improvement and matrix anabolism. Specifically, an increase in the expression of CD90, the marker of mesenchymal stem cells (MSCs), in the cartilage was observed. In addition, we evaluated the migratory and chondrogenic effects of CA on MSCs. Different concentration of CA was added to C3H10 T1/2 cells. The results showed that CA enhanced cell migration and chondrogenesis without affecting proliferation. Collectively, our findings indicate that CA may be effective for the treatment of cartilage defects via stimulation of endogenous MSCs.

Asunto(s)

Enfermedades de los Cartílagos , Cartílago Articular , Glucósidos Iridoides , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Animales , Ratones , Cartílago Articular/patología , Microtomografía por Rayos X , Diferenciación Celular , Enfermedades de los Cartílagos/metabolismo , Trasplante de Células Madre Mesenquimatosas/métodos , Condrogénesis

RESUMEN

A cell's most significant existential task is to survive by ensuring proper metabolism, avoiding harmful stimuli, and adapting to changing environments. It explains why early evolutionary primordial signals and pathways remained active and regulate cell and tissue integrity. This requires energy supply and a balanced redox state. To meet these requirements, the universal intracellular energy transporter purine nucleotide-adenosine triphosphate (ATP) became an important signaling molecule and precursor of purinergic signaling after being released into extracellular space. Similarly, ancient proteins involved in intracellular metabolism gave rise to the third protein component (C3) of the complement cascade (ComC), a soluble arm of innate immunity. These pathways induce cytosol reactive oxygen (ROS) and reactive nitrogen species (RNS) that regulate the redox state of the cells. While low levels of ROS and RNS promote cell growth and differentiation, supra-physiological concentrations can lead to cell damage by pyroptosis. This balance explains the impact of purinergic signaling and innate immunity on cell metabolism, organogenesis, and tissue development. Subsequently, along with evolution, new regulatory cues emerge in the form of growth factors, cytokines, chemokines, and bioactive lipids. However, their expression is still modulated by both primordial signaling pathways. This review will focus on the data that purinergic signaling and innate immunity carry on their ancient developmental task in hematopoiesis and specification of hematopoietic stem/progenitor cells (HSPCs). Moreover, recent evidence shows both these regulatory pathways operate in a paracrine manner and inside HSPCs at the autocrine level.

Asunto(s)

Células Madre Hematopoyéticas , Inmunidad Innata , Especies Reactivas de Oxígeno/metabolismo , Activación de Complemento , Hematopoyesis

RESUMEN

BACKGROUND AND AIMS: The G protein coupled receptor GPR15 is expressed on and functionally important for T cells homing to the large intestine. However, the precise mechanisms by which GPR15 controls gut homing have been unclear. Thus, we aimed to elucidate these mechanisms as well as to explore the potential of targeting GPR15 for interfering with T cell recruitment to the colon in inflammatory bowel disease [IBD]. METHODS: We used dynamic adhesion and transmigration assays, as well as a humanised in vivo model of intestinal cell trafficking, to study GPR15-dependent effects on gut homing. Moreover, we analysed GPR15 and integrin expression in patients with and without IBD, cross-sectionally and longitudinally. RESULTS: GPR15 controlled T cell adhesion to MAdCAM-1 and VCAM-1 upstream of α4ß7 and α4ß1 integrin, respectively. Consistently, high co-expression of these integrins with GPR15 was found on T cells from patients with IBD, and GPR15 also promoted T cell recruitment to the colon in humanised mice. Anti-GPR15 antibodies effectively blocked T cell gut homing in vitro and in vivo. In vitro data, as well as observations in a cohort of patients treated with vedolizumab, suggest that this might be more effective than inhibiting α4ß7. CONCLUSIONS: GPR15 seems to have a broad, but organ-selective, impact on T cell trafficking and is therefore a promising target for future therapy of IBD. Further studies are needed.

Asunto(s)

Adhesión Celular , Enfermedades Inflamatorias del Intestino , Mucoproteínas , Receptores Acoplados a Proteínas G , Linfocitos T , Receptores Acoplados a Proteínas G/metabolismo , Animales , Humanos , Ratones , Linfocitos T/metabolismo , Linfocitos T/inmunología , Mucoproteínas/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Adhesión Celular/efectos de los fármacos , Integrinas/metabolismo , Movimiento Celular , Moléculas de Adhesión Celular/metabolismo , Colon/metabolismo , Anticuerpos Monoclonales Humanizados/farmacología , Integrina alfa4beta1/metabolismo , Inmunoglobulinas/metabolismo , Femenino , Receptores de Péptidos

RESUMEN

In view of inevitable recurrences despite resection, glioblastoma (GB) is still an unmet clinical need. Dealing with the stromal-cell derived factor 1-alpha (SDF-1α)/CXCR4 axis as a hallmark of infiltrative GB tumors and with the resection cavity situation, the present study described the effects and relevance of a new engineered micro-nanostructured SF-HA-Hep aerogel sponges, made of silk fibroin (SF), hyaluronic acid (HA) and heparin (Hep) and loaded with SDF-1α, to interfere with the GB ecosystem and residual GB cells, attracting and confining them in a controlled area before elimination. 70 µm-pore sponges were designed as an implantable scaffold to trap GB cells. They presented shape memory and fit brain cavities. Histological results after implantation in brain immunocompetent Fischer rats revealed that SF-HA-Hep sponges are well tolerated for more than 3 months while moderately and reversibly colonized by immuno-inflammatory cells. The use of human U87MG GB cells overexpressing the CXCR4 receptor (U87MG-CXCR4+) and responding to SDF-1α allowed demonstrating directional GB cell attraction and colonization of the device in vitro and in vivo in orthotopic resection cavities in Nude rats. Not modifying global survival, aerogel sponge implantation strongly shaped U87MG-CXCR4+ tumors in cavities in contrast to random infiltrative growth in controls. Overall, those results support the interest of SF-HA-Hep sponges as modifiers of the GB ecosystem dynamics acting as "cell meeting rooms" and biocompatible niches whose properties deserve to be considered toward the development of new clinical procedures. STATEMENT OF SIGNIFICANCE: Brain tumor glioblastoma (GB) is one of the worst unmet clinical needs. To prevent the relapse in the resection cavity situation, new implantable biopolymer aerogel sponges loaded with a chemoattractant molecule were designed and preclinically tested as a prototype targeting the interaction between the initial tumor location and its attraction by the peritumoral environment. While not modifying global survival, biocompatible SDF1-loaded hyaluronic acid and silk fibroin sponges induce directional GB cell attraction and colonization in vitro and in rats in vivo. Interestingly, they strongly shaped GB tumors in contrast to random infiltrative growth in controls. These results provide original findings on application of exogenous engineered niches that shape tumors and serve as cell meeting rooms for further clinical developments.

Asunto(s)

Neoplasias Encefálicas , Fibroínas , Glioblastoma , Ratas , Humanos , Animales , Quimiocina CXCL12/farmacología , Fibroínas/farmacología , Ácido Hialurónico/farmacología , Ecosistema , Recurrencia Local de Neoplasia , Neoplasias Encefálicas/cirugía , Receptores CXCR4

RESUMEN

Mesenchymal stromal cells (MSCs) and chimeric antigen receptor (CAR)-T cells are two core elements in cell therapy procedures. MSCs have significant immunomodulatory effects that alleviate inflammation in the tissue regeneration process, while administration of specific chemokines and adhesive molecules would primarily facilitate CAR-T cell trafficking into solid tumors. Multiple parameters affect cell homing, including the recipient's age, the number of cell passages, proper cell culture, and the delivery method. In addition, several chemokines are involved in the tumor microenvironment, affecting the homing procedure. This review discusses parameters that improve the efficiency of cell homing and significant cell therapy challenges. Emerging comprehensive mechanistic strategies such as non-systemic and systemic homing that revealed a significant role in cell therapy remodeling were also reviewed. Finally, the primary implications for the development of combination therapies that incorporate both MSCs and CAR-T cells for cancer treatment were discussed.

Asunto(s)

Células Madre Mesenquimatosas , Neoplasias , Humanos , Medicina Regenerativa/métodos , Neoplasias/terapia , Linfocitos T , Quimiocinas , Microambiente Tumoral , Inmunoterapia Adoptiva/métodos

RESUMEN

Introduction: What if we changed our point of view? What if we approached endodontics from a biological perspective rather than a mechanistic one? What if, in the case of pulpal tissue necrosis, we were to consider an alternative to apexification therapies? Is pulp tissue regeneration now possible? Objective: Regenerative endodontic therapy (RET) aims to regenerate the pulp-dentin complex damaged by infection, trauma, or developmental anomaly of immature permanent teeth with necrotic pulp. The new intracanal tissue formation is expected to display pulp-like architecture and functions. There are two different based to tissue engineering approaches described to perform RET: cell-free CF-RET that attempt to induce host endogenous cells or stem cells to migrate into the root canal for regeneration or cell-based CB-RET which introduce exogenously prepared cells or stem cells into the canal for regeneration. Material and Method: CB-RET is the basis of current protocols recommended by the American Association of Endodontists (AAE) and the European Society of Endodontology (ESE) for the treatment of necrotic immature permanent teeth, with or without LIPOE. In this article, after defining the above-mentioned concepts, we will describe the ESE protocol and discuss the key steps for "getting started with endodontic regeneration". Conclusion: Each stage of the protocol must be carried out rigorously so as not to compromise the stages of the various biological processes involved. The practitioner has to stay informed of advances in knowledge resulting from research and new protocols to be published.

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Introduction: Et si nous changions de point de vue ? Et si nous abordions l'endodontie d'un point de vue biologique et non mécanistique ? Et si, devant la nécrose du tissu pulpaire, nous envisagions une alternative aux thérapeutiques d'apexification ? La régénération du tissu pulpaire est-elle désormais possible ? Objectif: L'objectif des thérapeutiques régénératives endodontiques (regenerative endodontic therapy ou RET) est de récréer au sein du canal radiculaire un tissu semblable au complexe dentino-pulpaire tant sur le point de l'organisation cellulaire que sur le point fonctionnel. Deux concepts basés sur les principes de l'ingénierie tissulaire sont décrits : l'un basé sur la transplantation de cellules souches : le CB-RET (Cell-based RET) et l'autre basé sur le cell homing, c'est-à-dire sur le recrutement de cellules souches localisées à proximité de l'apex : le CF-RET (Cell-free RET). Matériel et méthode: Les protocoles actuels recommandés par l'Association Américaine des Endodontistes (American Association of Endodontists ou AAE) et la Société Européenne d'Endodontie (European Society of Endodontology ou ESE) dans le traitement des dents permanentes immatures nécrosées en présence ou non de lésion inflammatoire périapicale d'origine endodontique (LIPOE) sont basés sur le CF-RET. Dans cet article, après avoir défini les concepts cités précédemment, nous décrirons le protocole de l'ESE et discuterons des étapes clés pour « se mettre à la régénération endodontique ¼. Conclusion: Chaque étape du protocole doit être conduite avec rigueur afin de ne pas compromettre les étapes des différents processus biologiques engagés. Le praticien devra se tenir informé des avancées des connaissances issues des travaux de recherche et des nouveaux protocoles qui seront édités.

Asunto(s)

Endodoncia , Endodoncia Regenerativa , Humanos , Pulpa Dental , Regeneración , Atención Odontológica , Necrosis de la Pulpa Dental/terapia

RESUMEN

Nonoperative treatments for Stress Urinary Incontinence (SUI) represent an ideal treatment method. Mesenchymal stem cell (MSCs) treatment is a new modality, but there is a lack of research in the field of gynecological pelvic floor and no good method to induce internal MSC homing to improve SUI. Herein, we develop an injectable and self-healing hydrogel derived from ß-chitin which consists of an amino group of quaternized ß-chitin (QC) and an aldehyde group of oxidized dextran (OD) between the dynamic Schiff base linkage.it can carry bFGF and SDF-1a and be injected into the vaginal forearm of mice in a non-invasive manner. It provides sling-like physical support to the anterior vaginal wall in the early stages. In the later stage, it slowly releasing factors and promoting the homing of MSCs in vivo, which can improve the local microenvironment, increase collagen deposition, repair the tissue around urethra and finally improve SUI (Scheme 1). This is the first bold attempt in the field of pelvic floor using hydrogel mechanical support combined with MSCs homing and the first application of chitin hydrogel in gynecology. We think the regenerative medicine approach based on bFGF/SDF-1/chitin hydrogel may be an effective non-surgical approach to combat clinical SUI.

Asunto(s)

Células Madre Mesenquimatosas , Incontinencia Urinaria de Esfuerzo , Femenino , Ratones , Animales , Hidrogeles/farmacología , Quitina/farmacología , Incontinencia Urinaria de Esfuerzo/tratamiento farmacológico , Colágeno

RESUMEN

BACKGROUND: Therapeutic strategies for patients with ulcerative colitis (UC) are based on patient- and disease-related factors in combination with drug characteristics but fail to predict success in individual patients. A considerable proportion of UC patients do not respond to the biological vedolizumab. Therefore, pretreatment biomarkers for therapeutic efficacy are urgently needed. Mucosal markers related to the integrin-dependent T lymphocyte homing could be potent predictors. METHODS: We prospectively included 21 biological- and steroid-naive UC patients with moderate-to-severe disease activity planned to escalate therapy to vedolizumab. At week 0, before initiating treatment, colonic biopsy specimens were obtained for immunophenotyping and immunohistochemistry. Clinical and endoscopic disease activity were determined at week 16 after 4 infusions of vedolizumab. In addition, we retrospectively included 5 UC patients who were first treated with anti-tumor necrosis factor α before receiving vedolizumab to compare with biological-naive patients. RESULTS: Abundance of α4ß7 on more than 8% of all CD3+ T lymphocytes in colonic biopsies at baseline was predictive for responsiveness to vedolizumab (sensitivity 100%, specificity 100%). The threshold for the proportion of MAdCAM-1+ and PNAd+ of all venules in the biopsies predictive for responsiveness to vedolizumab was ≥2.59% (sensitivity 89%, specificity 100%) and ≥2.41% (sensitivity 61%, specificity 50%), respectively. At week 16, a significant decrease of α4ß7+CD3+T lymphocytes was demonstrated in responders (18% [12%-24%] to 8% [3%-9%]; P = .002), while no difference was seen in nonresponders (4% [3%-6%] to 3%; P = .59). CONCLUSIONS: UC responders to vedolizumab have a higher percentage of α4ß7+CD3+ T lymphocytes and a higher proportion of MAdCAM-1+ venules in colonic biopsies than nonresponders before initiating therapy. Both analyses could be promising predictive biomarkers for therapeutic response and may lead to more patient tailored treatment in the future.

RESUMEN

While combination therapy completely suppresses HIV-1 replication in blood, functional virus persists in CD4+ T cell subsets in non-peripheral compartments that are not easily accessible. To fill this gap, we investigated tissue-homing properties of cells that transiently appear in the circulating blood. Through cell separation and in vitro stimulation, the HIV-1 "Gag and Envelope reactivation co-detection assay" (GERDA) enables sensitive detection of Gag+/Env+ protein-expressing cells down to about one cell per million using flow cytometry. By associating GERDA with proviral DNA and polyA-RNA transcripts, we corroborate the presence and functionality of HIV-1 in critical body compartments utilizing t-distributed stochastic neighbor embedding (tSNE) and density-based spatial clustering of applications with noise (DBSCAN) clustering with low viral activity in circulating cells early after diagnosis. We demonstrate transcriptional HIV-1 reactivation at any time, potentially giving rise to intact, infectious particles. With single-cell level resolution, GERDA attributes virus production to lymph-node-homing cells with central memory T cells (TCMs) as main players, critical for HIV-1 reservoir eradication.

Asunto(s)

Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , VIH-1/genética , Linfocitos T CD4-Positivos , Subgrupos de Linfocitos T

RESUMEN

Hematopoiesis is regulated by several mediators such as peptide-based growth factors, cytokines, and chemokines, whose biological effects have been studied for many years. However, several other mediators have been identified recently that affect the fate of hematopoietic stem/progenitor cells (HSPC) as well as non-hematopoietic cells in the bone marrow microenvironment. These new mediators comprise members of purinergic signaling pathways and are active mediators of the soluble arm of innate immunity, the complement cascade (ComC). In this review, we will discuss the coordinated effects of these pathways in regulating the biology of HSPC. Importantly, both purinergic signaling and the ComC are activated in stress situations and interact with specific receptors expressed on HSPC. Evidence has accumulated indicating that some of the purinergic as well as ComC receptors could also be activated intracellularly by intrinsically expressed ligands. To support this recent evidence, our work indicates that the major mediator of purinergic signaling, adenosine triphosphate, and the cleavage product of the fifth component of the ComC (C5), C5a anaphylatoxin, can activate their corresponding receptors expressed on the outer mitochondrial membrane in an autocrine manner. We will also discuss recent evidence that these responses, mediated by purinergic signaling and the ComC network, are coordinated by activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 - reactive oxygen species - NLR family pyrin domain containing 3 (NLRP3) inflammasome (Nox2-ROS-NLRP3) axis.

RESUMEN

The periosteum plays a key role in bone tissue regeneration, especially in the promotion and protection of new bones. However, among the bone repair materials, many biomimetic artificial periosteum lack the natural periosteal structure, stem cells, and immunoregulation required for bone regeneration. In this study, we used natural periosteum to produce acellular periosteum. To retain the appropriate cell survival structure and immunomodulatory proteins, we grafted the functional polypeptide SKP on the surface collagen of the periosteum via an amide bond, providing the acellular periosteum with the ability to recruit mesenchymal stem cells. Thus, we developed a biomimetic periosteum (DP-SKP) with the ability to promote stem cell homing and immunoregulation in vivo. Compared to the blank and simple decellularized periosteum groups, DP-SKP was more conducive to stem cell adhesion, growth, and osteogenic differentiation in vitro. Additionally, compared with the other two groups, DP-SKP significantly promoted mesenchymal stem cell homing to the periosteal transplantation site, improved the bone immune microenvironment, and accelerated new lamellar bone formation in the critical size defect of rabbit skulls in vivo. Therefore, this acellular periosteum with a mesenchymal stem cell homing effect is expected to be used as an extracellular artificial periosteum in clinical practice.

Asunto(s)

Células Madre Mesenquimatosas , Periostio , Animales , Conejos , Osteogénesis , Células Madre , Amidas