The regenerative medicine in oral and maxillofacial surgery: The most important innovations in the clinical application of mesenchymal stem cells

Regenerative medicine is an emerging field of biotechnology that combines various aspects of medicine, cell and molecular biology, materials science and bioengineering in order to regenerate, repair or replace tissues.The oral surgery and maxillofacial surgery have a role in the treatment of traumatic or degenerative diseases that lead to a tissue loss: frequently, to rehabilitate these minuses, you should use techniques that have been improved over time. Since 1990, we started with the use of growth factors and platelet concentrates in oral and maxillofacial surgery; in the following period we start to use biomaterials, as well as several type of scaffolds and autologous tissues. The frontier of regenerative medicine nowadays is represented by the mesenchymal stem cells (MSCs): overcoming the ethical problems thanks to the use of mesenchymal stem cells from adult patient, and with the increasingly sophisticated technology to support their manipulation, MSCs are undoubtedly the future of medicine regenerative and they are showing perspectives unimaginable just a few years ago. Most recent studies are aimed to tissues regeneration using MSCs taken from sites that are even more accessible and rich in stem cells: the oral cavity turned out to be an important source of MSCs with the advantage to be easily accessible to the surgeon, thus avoiding to increase the morbidity of the patient.The future is the regeneration of whole organs or biological systems consisting of many different tissues, starting from an initial stem cell line, perhaps using innovative scaffolds together with the nano-engineering of biological tissues

Odontogenic differentiation of human dental pulp stem cells on hydrogel scaffolds derived from decellularized bone extracellular matrix and collagen type I

Objectives: The aim of this study was to evaluate the level of odontogenic differentiation of dental pulp stem cells (DPSCs) on hydrogel scaffolds derived from bone extracellular matrix (bECM) in comparison to those seeded on collagen I (Col-I), one of the main components of dental pulp ECM. Methods: DPSCs isolated from human third molars were characterized for surface marker expression and odontogenic potential prior to seeding into bECM or Col-I hydrogel scaffolds. The cells were then seeded onto bECM and Col-I hydrogel scaffolds and cultured under basal conditions or with odontogenic and growth factor (GF) supplements. DPSCs cultivated on tissue culture polystyrene (TCPS) with and without supplements were used as controls. Gene expression of dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP-1) and matrix extracellular phosphoglycoprotein (MEPE) was evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and mineral deposition was observed by Von Kossa staining. Results: When DPSCs were cultured on bECM hydrogels, the mRNA expression levels of DSPP, DMP-1 and MEPE genes were significantly upregulated with respect to those cultured on Col-I scaffolds or TCPS in the absence of extra odontogenic inducers. In addition, more mineral deposition was observed on bECM hydrogel scaffolds as demonstrated by Von Kossa staining. Moreover, DSPP, DMP-1 and MEPE mRNA expressions of DPSCs cultured on bECM hydrogels were further upregulated by the addition of GFs or osteo/odontogenic medium compared to Col-I treated cells in the same culture conditions. Significance: These results demonstrate the potential of the bECM hydrogel scaffolds to stimulate odontogenic differentiation of DPSCs

Tip-Clearance Actuation With Magnetic Bearings for High-Speed Compressor Stall Control

Magnetic bearings are widely used as active suspension devices in rotating machinery, mainly for active vibration control purposes. The concept of active tip clearance control suggests a new application of magnetic bearings as servo-actuators to stabilize rotating stall in axial compressors. This paper presents a first-of-a-kind feasibility study of an active stall control experiment with a magnetic bearing servo-actuator in the NASA Glenn high-speed single-stage compressor test facility. Together with CFD and experimental data a two-dimensional, incompressible compressor stability model was used in a stochastic estimation and control analysis to determine the required magnetic bearing performance for compressor stall control. The resulting requirements introduced new challenges to the magnetic bearing actuator design. A magnetic bearing servo-actuator was designed which fulfilled the performance specifications. Control laws were then developed to stabilize the compressor shaft. In a second control loop, a constant gain controller was implemented to stabilize rotating stall. A detailed closed loop simulation at 100% corrected design speed resulted in a 2.3% reduction of stalling mass flow which is comparable to results obtained in the same compressor by Weigl et al. (1998) using unsteady air injection. The design and simulation results presented here establish the viability of magnetic bearings for stall control in aero-engine high-speed compressors. Furthermore the paper outlines a general design procedure to develop magnetic bearing servo-actuators for high-speed turbomachinery.United States. National Aeronautics and Space Administration (Grant NAG3-1457

Chemical behavior and in vitro activity of mixed phosphine gold(I)compounds on melanoma cell lines.

7partially_openCARUSO F; PETTINARI C; PADUANO F; VILLA R; MARCHETTI F; E. MONTI; ROSSI MCaruso, F; Pettinari, C; Paduano, F; Villa, R; Marchetti, F; Monti, ELENA CATERINA; Rossi, M

Mechanical influence of tissue culture plates and extracellular matrix on mesenchymal stem cell behavior: A topical review

Tissue engineering applications need a continuous development of new biomaterials able to generate an ideal cell-extracellular matrix interaction. The stem cell fate is regulated by several factors, such as growth factors or transcription factors. The most recent literature has reported several publications able to demonstrate that environmental factors also contribute to the regulation of stem cell behavior, leading to the opinion that the environment plays the major role in the cell differentiation. The interaction between mesenchymal stem cells (MSCs) and extracellular environment has been widely described, and it has a crucial role in regulating the cell phenotype. In our laboratory (Tecnologica Research Institute, Crotone, Italy), we have recently studied how several physical factors influence the distribution and the morphology of MSCs isolated from dental pulp, and how they are able to regulate stem cell differentiation. Mechanical and geometrical factors are only a small part of the environmental factors able to influence stem cell behavior, however, this influence should be properly known: in fact, this assumption must be clearly considered during those studies involving MSCs; furthermore, these interactions should be considered as an important bias that involves an high number of studies on the MSCs, since in worldwide laboratories the scientists mostly use tissue culture plates for their experiments

A Vegetation and Fire History of Lake Titicaca since the Last Glacial Maximum

Fine-resolution fossil pollen and charcoal analyses reconstruct a vegetation and fire history in the area surrounding Lake Titicaca (3810 m, Peru/Bolivia) since ca. 27,500 cal yr BP (hereafter BP). Time control was based on 26 accelerator mass spectrometer (AMS) radiocarbon dates. Seventeen AMS dates and 155 pollen and charcoal samples between ca. 17,500 BP and ca. 3,100 BP allow a centennial-scale reconstruction of deglacial and early- to mid-Holocene events. Local and regional fire signals were based on the separation of two charcoal size fractions, ≥180 μm and 179–65 μm. Charcoal abundance correlated closely with the proportion of woody taxa present in the pollen spectra. Little or no pollen was detected in the sedimentary record prior to ca. 21,000 BP. Very cold climatic conditions prevailed, with temperatures suggested to be at least 5–8°C cooler than present. Increases in pollen concentration suggest initial warming at ca. 21,000 BP with a more significant transition toward deglaciation ca. 17,700 BP. Between 17,700 BP and 13,700 BP, puna brava is progressively replaced by puna and sub-puna elements. The most significant changes between the Pleistocene and the Holocene floras were largely complete by 13,700 BP, providing an effective onset of near-modern conditions markedly earlier than in other Andean records. Fire first occurs in the catchment at ca. 17,700 BP and becomes progressively more important as fuel loads increase. No evidence is found of a rapid cooling and warming coincident with the Younger Dryas chron. A dry event between ca. 9,000 BP and 3,100 BP, with a peak between 6,000 and 4,000 BP, is inferred from changes in the composition of aquatics, and the marsh community as pollen of Cyperaceae is replaced by Poaceae, Apiaceae, Plantago and the shrub Polylepis. Human disturbance of the landscape is evident in the pollen spectra after ca. 3,100 BP with the appearance of weed species

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

In this review we have showcased the preclinical development of original amphiphilic nanomaterials designed for ruthenium-based anticancer treatments, to be placed within the current metallodrugs approach leading over the past decade to advanced multitarget agents endowed with limited toxicity and resistance. This strategy could allow for new options for breast cancer (BC) interventions, including the triple-negative subtype (TNBC) with poor therapeutic alternatives. BC is currently the second most widespread cancer and the primary cause of cancer death in women. Hence, the availability of novel chemotherapeutic weapons is a basic requirement to fight BC subtypes. Anticancer drugs based on ruthenium are among the most explored and advanced next-generation metallotherapeutics, with NAMI-A and KP1019 as two iconic ruthenium complexes having undergone clinical trials. In addition, many nanomaterial Ru complexes have been recently conceived and developed into anticancer drugs demonstrating attractive properties. In this field, we focused on the evaluation of a Ru(III) complex-named AziRu-incorporated into a suite of both zwitterionic and cationic nucleolipid nanosystems, which proved to be very effective for the in vivo targeting of breast cancer cells (BBC). Mechanisms of action have been widely explored in the context of preclinical evaluations in vitro, highlighting a multitarget action on cell death pathways which are typically deregulated in neoplasms onset and progression. Moreover, being AziRu inspired by the well-known NAMI-A complex, information on non-nanostructured Ru-based anticancer agents have been included in a precise manner

Polymerized mixed aggregates containing gadolinium complex and CCK8 peptide.

Two novel amphiphilic unimers contg. an aliph. hydrophobic chain (PDA) with two C C triple bonds and hydrophilic heads presenting the chelating agent DTPAGlu and the CCK8 bioactive peptide, resp., have been prepd. by solid phase synthesis. Aggregates obtained by mixing together PDA-DTPAGlu, or its Gd(III) complex, and PDA-L2-CCK8 in 70/30 molar ratio before and after a polymn. process carried out by UV irradn. have been structurally characterized by means of small angle neutron scattering. The relaxivity properties of aggregates contg. Gadolinium complexes have also been investigated. Elongated mixed micelles have been obsd., in which the relaxivity value r1p for each Gadolinium complex, measured at 20 MHz and 298 K, is around 12 mM-1s-1

A thermodynamic signature of lipid segregation in biomembranes induced by a short peptide derived from glycoprotein gp36 of feline immunodeficiency virus.

The interactions between proteins/peptides and lipid bilayers are fundamental in a variety of key biological processes, and among these, the membrane fusion process operated by viral glycoproteins is one of the most important, being a fundamental step of the infectious event. In the case of the feline immunodeficiency virus (FIV), a small region of the membrane proximal external region (MPER) of the glycoprotein gp36 has been demonstrated to be necessary for the infection to occur, being able to destabilize the membranes to be fused. In this study, we report a physicochemical characterization of the interaction process between an eight-residue peptide, named C8, modeled on that gp36 region and some biological membrane models (liposomes) by using calorimetric and spectroscopic measurements. CD studies have shown that the peptide conformation changes upon binding to the liposomes. Interestingly, the peptide folds from a disordered structure (in the absence of liposomes) to a more ordered structure with a low but significant helix content. Isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) results show that C8 binds with high affinity the lipid bilayers and induces a significant perturbation/reorganization of the lipid membrane structure. The type and the extent of such membrane reorganization depend on the membrane composition. These findings provide interesting insights into the role of this short peptide fragment in the mechanism of virus-cell fusion, demonstrating its ability to induce lipid segregation in biomembranes

Exosomes from human periapical Cyst-MSCs: Theranostic application in Parkinson’s disease

The scientific community continuously strives to get new disease models, to discover early markers or novel therapeutic approaches, improving the diagnosis and prognosis of several human pathologies. Parkinson’s Disease (PD) is characterized by a long asymptomatic phase, characterized by a selective loss of dopaminergic neurons. Recently, the human Periapical Cyst-Mesenchymal Stem Cells (hPCy-MSCs) have been differentiated in functional dopaminergic neurons: such oral-derived MSCs and the hPCy-MSCs-derived exosomes may represent a strategic and useful in vitro study-model, as well as intriguing therapeutic carriers. Circadian rhythm (CR) alteration variously impacts on PD pathways: an interesting research target is represented by the analysis of the exosomes released by dopaminergic neurons, derived from neural-differentiated hPCy-MSCs, after having reproduced in-vitro PD-like conditions. This review aims to describe the crosstalk among some aspects of circadian rhythm related to the onset of PD and the exosomes released by cells of PD patients. More in detail: the first part of this article will describe the main characteristics of circadian rhythm and the involvement of the exosomes found to be effective in the pathogenesis of PD. Finally, the authors will suggest how those exosomes derived from dopaminergic neurons, obtained by oral-derived stem cells (hPCy-MSCs) may represent a smart model for the in vitro research on PD, to find new biomarkers, to test new drugs or, fatally, to find new pathways applicable in future therapeutic approaches