Allogeneic Adipose-Derived Mesenchymal Stromal Cells Ameliorate Experimental Autoimmune Encephalomyelitis by Regulating Self-Reactive T Cell Responses and Dendritic Cell Function

Multipotent mesenchymal stromal cells (MSCs) have emerged as a promising therapy for autoimmune diseases, including multiple sclerosis (MS). Administration of MSCs to MS patients has proven safe with signs of immunomodulation but their therapeutic efficacy remains low. The aim of the current study has been to further characterize the immunomodulatory mechanisms of adipose tissue-derived MSCs (ASCs) in vitro and in vivo using the EAE model of chronic brain inflammation in mice. We found that murine ASCs (mASCs) suppress T cell proliferation in vitro via inducible nitric oxide synthase (iNOS) and cyclooxygenase- (COX-) 1/2 activities. mASCs also prevented the lipopolysaccharide- (LPS-) induced maturation of dendritic cells (DCs) in vitro. The addition of the COX-1/2 inhibitor indomethacin, but not the iNOS inhibitor L-NAME, reversed the block in DC maturation implicating prostaglandin (PG) E2 in this process. In vivo, early administration of murine and human ASCs (hASCs) ameliorated myelin oligodendrocyte protein- (MOG35-55-) induced EAE in C57Bl/6 mice. Mechanistic studies showed that mASCs suppressed the function of autoantigen-specific T cells and also decreased the frequency of activated (CD11c+ and CD11c+TNF-α+) DCs in draining lymph nodes (DLNs). In summary, these data suggest that mASCs reduce EAE severity, in part, through the impairment of DC and T cell function.This work has been financed by the Instituto de Salud Carlos III, Spain (http://www.isciii.es) and Fondo Europeo de Desarrollo Regional (FEDER, http://ec.europa.eu/regional_policy/es/funding/erdf/) from the European Union, through the Research Grants PI15/00794, CP09/00228, and CPII15/00032 (Per Anderson); PI12/01097, PI15/02015, and ISCIII Red de Terapia Celular (RD12/0019/0006, http://www.red-tercel.com/) (Francisco Martin); and PS09-00928 (Mario Delgado). Mario Delgado was supported by a grant (PSE-010000-2009-3) from the Ministerio de Ciencia e Innovación, Spain (http://www.idi.mineco.gob.es/), and P09-CTS-4723 from the Junta de Andalucia (Proyecto de Excelencia). Francisco Martin is funded by the Fundación Progreso y Salud (Consejería de Salud, Junta de Andalucía, http://www.juntadeandalucia.es/fundacionprogresoysalud/)

Sauvé-Kapandji and reverse Sauvé-Kapandji procedures for treating chronic longitudinal radioulnar dissociation with capitellum fracture

Almost all reported cases of longitudinal radioulnar dissociation have involved fracture of the radial head, rupture of the interosseous membrane, and disruption of the distal radioulnar joint, although unusual patterns of Essex-Lopresti injury have also been described. To our knowledge, this is the first report of a chronic Essex-Lopresti variant including fracture of the capitellum. A displaced capitellum fracture must alert to the possibility of longitudinal radioulnar dissociation, even without concomitant radial head fracture or symptoms at the forearm and ulnar wrist. Successful mid-term results can be achieved by treating malunion of humeral condyle and proximal migration of the radius with simultaneous Sauvé-Kapandji procedure at the wrist and reverse Sauvé-Kapandji at the elbow.Essex-Lopresti lezyonlarının nadir görülen bazı atipik formları tanımlanmış olsa da, literatürde bildirilen longitudinal radioulnar instabilite olgularında genellikle radius başı kırığı ve proksimal ve distal radioulnar eklemlerde yaralanma söz konusudur. Bu çalışmada kapitellum kırığı ile birlikte Essex- Lopresti lezyonu olan bir hastayı bildiriyoruz. Olgumuzda el bileğinde Sauvé-Kapandji ve dirsekte ters Sauvé-Kapandji tekniklerinin kombine olarak uygulanması ile orta vadede başarılı sonuçlar alınmıştır. El bileği ve önkol yakınması olmasa bile deplase kapitellum kırıklı hastalarda longitudinal radioulnar instabilite akla getirilmelidir

PARP inhibition promotes endothelial-like traits in melanoma cells and modulates pericyte coverage dynamics during vasculogenic mimicry

Vasculogenic mimicry (VM) describes the ability of highly aggressive tumor cells to develop pseudovascular structures without the participation of endothelial cells. PARP1 is implicated in the activation of hypoxia-inducible factors, which are crucial in tumor neovascularization. We have explored the role of hypoxia and PARP inhibition in VM. In uveal melanoma xenografts, the PARP inhibitor olaparib improved in vivo pericyte coverage specifically of VM channels. This was concomitant with reduced metastasis in olaparib-treated VM+ tumors. PARP inhibition and hypoxia modulated melanoma tube formation in vitro, inducing a more sparse and regular tubular architecture. Wholetranscriptome profiling revealed that olaparib treatment under hypoxic conditions modulated the expression of genes implicated in vasculogenesis during tube formation, enhancing the endothelial-like phenotype of VM+ uveal melanoma cells. PARP inhibition, especially during hypoxia, upregulated PDGFβ, which is essential for pericyte recruitment. Our study indicates that PARP inhibitors may enhance the endothelial characteristics of VM+ cells, modulate pericyte coverage, and reduce metastatic spread in VM+ melanoma.Spanish Government Ministry of Science and Innovation, Spain (MICINN) Spanish Government SAF2015-70520-R RTI2018-098968-B-I00 RTICC RD12/0036/0026CIBER Cancer ISCIII CB16/12/00421Junta de Andalucia PY20_01179Fundacion Domingo Martine

Composite Alloplastic Biomaterial vs. Autologous Platelet-Rich Fibrin in Ridge Preservation

Aim: The aim of this study was to examine the clinical and histological differences of using a combination of alloplastic beta triphasic calcium phosphate (_ β-TCP) and a cross-linked collagen membrane versus autologous platelet-rich fibrin (PRF-L) in ridge preservation after dental extraction. Material and methods: Fifty-one patients were included in this observational case-series study. Dental extractions were performed, after which 25 patients were grafted with _-TCP and 26 with PRF-L. After four months of healing, clinical, radiological, histomorphometric and histological evaluations were performed. Results: A significantly higher percentage of mineralized tissue was observed in samples from the PRF-L grafted areas. Cellularity was higher in PRF-L grafted areas (osteocytes in newly formed bone per mm2 = 123.25 (5.12) vs. 84.02 (26.53) for PRF-L and β-TCP, respectively, p = 0.01). However, sockets grafted with PRF-L showed a higher reduction in the bucco-lingual dimension after four months of healing (2.19 (0.80) vs. 1.16 (0.55) mm, p < 0.001), as well as a higher alteration in the final position of the mid muco-gingival junction (1.73 (1.34) vs. 0.88 (0.88) mm, p < 0.01). Conclusion: PRF-L concentrate accelerates wound healing in post-extraction sockets in terms of new mineralized tissue component. However, the use of β-TCP biomaterial appears to be superior to maintain bucco-lingual volume and the final position of the muco-gingival junction.The authors of this manuscript were partially supported by Research Groups #CTS-138 (FO) and #CTS-1028 (PGM, MPM) (Junta de Andalucía, Spain). Grafting materials were generously provided by Dentium Co., Ltd., Seoul, Korea

The Influence of History of Severe Periodontitis on Estimated Long-Term Marginal Bone Loss around Implants Restored with Fixed Segmented Full-Arch Rehabilitation

The authors of this manuscript are partially supported by Research Groups #CTS-138, #CTS-176 and #CTS-1028 (Junta de Andalucía, Spain).The aim of this study was to analyze the long-term marginal bone level (MBL) of implants supporting fixed full-arch restoration in patients who had previously lost their dentition due to severe periodontitis. This retrospective study included 35 patients in whom 342 implants with internal tapered conical connections were placed. MBL was analyzed radiographically over time and a long-term estimation of MBL was calculated. A mixed linear model with abutment height, graft, diameter and location (maxilla/mandible) as factors and gender, age, implant length and prosthetic variables as covariates was used to evaluate the influence on MBL. MBL in these patients showed an estimator of predictions at 4108 days after loading of −0.307 mm, SE = 0.042. Only 0.15% of implants were radiographically affected with MBL of 3 mm or more. The mixed linear model results showed a main effect of the type of opposing dentition, gender, implant diameter, and abutment height. Particularly, an abutment height of 1 mm had associated larger MBL than the remaining heights. Thus, it can be concluded that dental implants restored with fixed segmented full-arch rehabilitation in patients with a history of severe periodontal disease do not suffer important marginal bone loss if some specific factors are considered, mainly the use of long transmucosal abutments (≥2 mm).Junta de Andalucía CTS-138, CTS-176, CTS-102

Neutrophil Extracellular Traps in Periodontitis

Neutrophils are key cells of the immune system and have a decisive role in fighting foreign pathogens in infectious diseases. Neutrophil extracellular traps (NETs) consist of a mesh of DNA enclosing antimicrobial peptides and histones that are released into extracellular space following neutrophil response to a wide range of stimuli, such as pathogens, host-derived mediators and drugs. Neutrophils can remain functional after NET formation and are important for periodontal homeostasis. Periodontitis is an inflammatory multifactorial disease caused by a dysbiosis state between the gingival microbiome and the immune response of the host. The pathogenesis of periodontitis includes an immune-inflammatory component in which impaired NET formation and/or elimination can be involved, contributing to an exacerbated inflammatory reaction and to the destruction of gingival tissue. In this review, we summarize the current knowledge about the role of NETs in the pathogenesis of periodontitis

Algae-derived hydroxyapatite behavior as bone biomaterial in comparison with anorganic bovine bone: A split-mouth clinical, radiological, and histologic randomized study in humans

This is the peer reviewed version of the following article: [Galindo-Moreno P, Padial-Molina M, Lopez-Chaichio L, Gutiérrez-Garrido L, Martín-Morales N, O'Valle F. Algae-derived hydroxyapatite behavior as bone biomaterial in comparison with anorganic bovine bone: A split-mouth clinical, radiological, and histologic randomized study in humans. Clin Oral Implants Res. 2020 Jun;31(6):536-548. doi: 10.1111/clr.13590. Epub 2020 Mar 6], which has been published in final form at [https://doi.org/10.1111/clr.13590]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.Objectives: To analyze a modified biphasic phycogenic biomaterial in comparison with anorganic bovine bone in maxillary sinus floor elevation in humans. Material and methods: Eight male patients in need of bilateral two-stage sinus floor elevation were consecutively recruited for this randomized split-mouth study. A combination of autogenous cortical bone (ACB, 20%) and anorganic bovine bone (ABB, 80%) (ACB + ABB group) or ACB (20%) and modified biphasic phycogenic material (BP, 80%) (ACB + BP group) were randomly assigned to graft each sinus. Patients were followed up for 6 months post-surgery when bone samples were collected for analysis. Results: Radiographically, bone height gain was statistically higher in the ACB + ABB versus the ACB + BP group. While the analysis of the biological compartments showed differences in non-mineralized tissue (39.15 ± 20.97% vs. 65.87 ± 28.59%, ACB + ABB vs. ACB + BP respectively; p = .018) and remnant biomaterial particles (22.62 ± 17.01% vs. 7.96 ± 8.57%, respectively; p = .028), the percentage of mineralized tissue (38.23 ± 17.55% vs. 24.14 ± 24.66%, respectively; p = .398) showed no statistically significant difference. In contrast, ACB + ABB biopsies showed higher Musashi-1-positive cells per mm2 compared to ACB + BP biopsies (811.49 ± 875.30 vs. 236.90 ± 280.81; p < .018), where the fusiform cells corresponded mainly with fibroblasts, as demonstrated by ultrastructural analysis. Conclusion: Both combinations of materials exhibited bone formation after 6 months of healing in the maxillary sinus cavity. However, the combination with biphasic phycogenic biomaterial induced a higher radiographical vertical resorption and graft collapse in comparison with the combination with anorganic bovine bone, possibly due to a higher remodeling of the graft.Junta de Andalucía #CTS-138 and #CTS-102

Bacteria associated with periodontal disease are also increased in health

The objective of this cross-sectional clinical study was to analyze the differences in the microbiome in gingival sulci of adult patients in the presence or absence of chronic periodontitis. Patients with or without periodontal disease were included in this cross-sectional study. Subgingival biofilm samples were collected and analyzed by 16S massive pyrosequencing. Functional analyses were also performed. A total of 15 phyla, 154 genera and 351 species were detected globally. Differences between disease and non-disease samples were observed in all taxonomical levels which suggest functional profile changes in the community. It was found that the main species associated with non-disease samples were reduced in disease but not completely suppressed. Analysis of the functional potential of the biofilms revealed a significantly higher activity related to endocytosis and phosphatidylinositol signaling in the disease group but lower cell adhesion molecules. Specific differences between health and disease suggest functional profile changes in the community, although bacteria associated with periodontal disease are also increased in health. Transcriptome studies should be conducted to confirm and deepen metabolic dysfunctions

Maxillary sinus dimensions with respect to the posterior superior alveolar artery decrease with tooth loss

Background: The posterior superior alveolar (PSA) artery is frequently encountered in the area where the lateral osteotomy is performed during direct sinus augmentation procedures. Objective: To investigate the correlation between patient-dependent variables and measurements related to PSA using cone beam computed tomography (CBCT) data. Methods: Three hundred ninety-four CBCT scans were evaluated to assess the PSA artery diameter and distances to the sinus floor and to alveolar crest. Patient's age, gender, and edentulism status were recorded. Results: The PSA artery tends to be wider in older patients. Distances to the sinus floor or the alveolar crest tend to be shorter in women and in partially and completely edentulous patients. Also, as those distances decrease, the mediolateral width of the sinus increases. Conclusion: Tooth loss leads to maxillary sinus vertical collapse with respect to the PSA artery. The position of the artery is stable; so, the mediolateral dimensions at different heights from the floor increase. Practical implications: The reduced distances from the PSA to the sinus floor and the alveolar crest in edentulous patients potentially increase the risk of injury during maxillary sinus lift. Additionally, when the distance to the sinus floor decreases, the mediolateral dimensions of the sinus at different heights increase, which may complicate the technique and challenge the outcomes.Junta de Andalucía #CTS-138 and #CTS-58

Bone Regeneration from PLGA Micro-Nanoparticles

Poly-lactic-co-glycolic acid (PLGA) is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2). Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed.The authors wish to express their appreciation for the financial support granted by the “Ministerio de Educación y Ciencia” (MEC, Spain), Projects MAT2013-43922-R, and Research Groups no. FQM-115, no. CTS-138, and no. CTS-583 (Junta de Andalucía, Spain). Partial support was also provided by the Andalucía Talent Hub Program from the Andalusian Knowledge Agency, cofunded by the European Union’s Seventh Framework Program, Marie Skłodowska-Curie actions (COFUND, Grant Agreement no. 291780) and the Ministry of Economy, Innovation, Science and Employment of the Junta de Andalucía (Miguel Padial-Molina)