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Age-related regenerative potential of human Dental Pulp Stem/Stromal Cells (hDPSCs): possible consequences in an ageing society
Full text linkIl trattamento efficace della pulpite e/o della parodontite continua ad essere una sfida nella pratica clinica soprattutto in relazione all’invecchiamento della popolazione. Quest’ultimo è un fenomeno fisiologico che si verifica con il tempo e che impedisce la normale funzionalità degli organi, ostacolando l'omeostasi dei tessuti e delle attività fisiologiche. Inoltre, è ben noto che le cellule senescenti influenzano significativamente il loro microambiente, poiché secernono molecole pro-infiammatorie e degradative. Gli approcci di medicina rigenerativa potrebbero soddisfare le necessità di nuove terapie per tali patologie e di conseguenza risulta importante poter valutare sia le ripercussioni legate età sulle potenzialità di Cellule Stromali/Staminali Mesenchimali (MSC) nonché gli effetti legati al microambiente.
Nello specifico, poiché le cellule Staminali/Stromali derivate dalla Polpa Dentale (DPSC) rappresentano un buon candidato per le terapie restaurative del cavo orale, lo studio del loro potenziale rigenerativo età correlato potrebbe essere fondamentale per lo sviluppo di trattamenti sempre più personalizzati in una società che invecchia.
I nostri studi in vitro sono stati inizialmente indirizzati a valutare i cambiamenti morfologici, proliferativi e differenziativi verso i fenotipi mesenchimali, odontoblastici e neuronali di cellule della polpa dentaria (hDPSC) isolate da soggetti di età diversa. Successivamente, abbiamo studiato gli effetti di un microambiente età correlato sul comportamento biologico di hDPSC ottenute sia da individui giovani che da soggetti anziani. Dalle analisi citofluorimetriche, immunoistochimiche, e di espressione genica mediante Real Time PCR (qRT-PCR) e western blotting è emerso un declino sia della capacità proliferativa che e del potenziale differenziativo con l'avanzare dell’età dei donatori. Inoltre, è stato possibile riscontrare modificazioni età correlate della capacità di mineralizzazione della matrice extracellulare in seguito a stimoli odontogenici e osteogenici. Anche il differenziamento in senso neuronale ha evidenziato cambiamenti età correlati. Infine, la presenza di un microambiente età-correlato ha mostrato effetti significativi sul comportamento di hDPSC isolate da soggetti giovani e anziani.
Successivamente, nell’ottica di combinare l'odontoiatria restaurativa convenzionale con le recenti tecniche rigenerative, si è voluta testare la biocompatibilità in vitro di un composito dentale nanoriempito di ultima generazione (Filtek Supreme XTE), comunemente usato in odontoiatria. Anche in questo caso sono stati analizzati la capacità proliferativa, l'apoptosi e il potenziale differenziativo in senso odontogenico delle hDPSC, nonché la loro capacità di mineralizzare la matrice. I nostri dati hanno dimostrato che Filtek Supreme XTE influenza e/o ritarda i processi di differenziamento e mineralizzazione della matrice da parte delle hDPSC rispetto ai controlli rappresentati sia cellule messe a contatto con la dentina sia da hDPSC coltivate in plastica. Questa sperimentazione preliminare, eseguita con cellule provenienti da individui giovani, pone le basi per futuri studi con cellule ottenute da soggetti anziani utili allo sviluppo di materiali bioattivi adatti ad una popolazione che invecchia.
In conclusione, i nostri studi hanno confermato che le caratteristiche biologiche delle hDPSC possono risultare compromesse dai fenomeni di invecchiamento, probabilmente anche in relazione a fattori presenti nel microambiente in grado di modulare l’attività cellulare. Queste osservazioni risultano utili per lo sviluppo di terapie personalizzate che mirano alla rigenerazione di osso, polpa dentaria e dentina, nonché per l’applicazione in medicina rigenerativa del trattamento di disturbi neurologici. Nell’ambito dell’odontoiatria conservativa, è da tenere inoltre in considerazione che l’esposizione a lungo termine delle hDPSC con i compositi nanoriempiti sulle potrebbe ritardare in modo significativo e perfino interrompere il loro di differenziamento in senso odontogenico e/o la mineralizzazione della matrice extracellulare. Questi dati sono di rilevanza clinica, poiché nelle lesioni traumatiche o cariose, le cellule della polpa potrebbero avere una ridotta capacità rigenerativa in un tessuto dentale vulnerabile, specialmente in un soggetto anziano.Uncomplicated dental treatments for pulpitis and periodontitis continues to be challenging especially in elderly, and regenerative approaches could meet this contingency. Ageing is a physiologic phenomenon occurring with time, which hamper the organs’ functional capacity that normally maintains tissue homeostasis and physiological responses. Moreover, it is well known that aged cells significantly affect their microenvironment, as they secrete pro-inflammatory and matrix-degrading molecules. The impact of these factors on Mesenchymal Stem/Stromal Cells (MSCs) could be also of interest for a better understanding of the age-related regenerative potential. Since Dental Pulp Stem/Stromal cells (DPSCs) represent a good candidate for oral restorative therapies, the study of age-related changes in their recovering capability could be crucial for developing customized treatments for an ageing society.
In our in vitro investigations, we firstly analysed changes in the morphology, proliferation, and differentiation toward mesenchymal, odontoblastic and neuronal phenotypes of human DPSCs (hDPSCs) harvested from differently aged donors. Then, we studied the effects of an age-related microenvironment on the biological performances of hDPSCs isolated from young and old subjects.
Cytofluorimetric, immunohistochemical, quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR), and western blot analyses were performed. We observed a decline in hDPSCs proliferation and differentiation potential with age. Moreover, these cells showed distinct age‐related mineralization capabilities as well as neurogenic differentiation. In addition, cell-conditioned media from an age-related microenvironment was able to modify the behaviour of hDPSCs isolated from young or old subjects.
Later, aimed to combine the conventional restorative dentistry with the recent regenerative techniques, the in vitro impact of a commonly used nanofilled composite (Filtek Supreme XTE) on hDPSCs was taken into account. In this research, proliferation, apoptosis, differentiation ability as well as matrix mineralization, of hDPSCs cultured in the presence of a nanofilled composite were examined. Our data demonstrated that Filtek Supreme XTE affects and delays hDPSCs differentiation and mineralization processes when compared to a control group with dentin-slices as well as in tissue culture plates. This initial approach performed with young cells paves the ways for future studies with hDPSCs derived from old subjects, in order to develop a bioactive material customised for an ageing population
In conclusion, our results confirmed that ageing differently impaired hDPSCs biological properties and local factors may modulate these processes. Our observations represent a valid tool for the development of tailored regenerative strategies in an ageing society
Synovium-derived stromal cell-induced osteoclastogenesis: a potential osteoarthritis trigger
Full text linkPurpose: To shed light on the idea that mesenchymal stem/stromal cells (MSCs) recruited in synovium (SM) (i.e. Synovium-Derived Stromal Cells, SDSCs) could be involved in Osteoarthritis (OA) pathophysiology. Attention was also paid to a further stromal cell type with a peculiar ultrastructure called telocytes (TCs), whose role is far from clarified. Methods: In the present in vitro study, we compared SDSCs isolated from healthy and OA subjects in terms of phenotype, morphology and differentiation potential as well as in their capability to activate normal Peripheral Blood Mononuclear Cells (PBMCs). Histological, immunohistochemical and ultrastructural analyses were integrated by qRT-PCR and functional resorbing assays. Results: Our data demonstrated that both SDSC populations stimulated the formation of osteoclasts from PBMCs: the osteoclast-like cells generated by healthy-SDSCs via transwell co-cultures were inactive, while OA-derived SDSCs have a much greater effectiveness. Moreover, the presence of TCs was more evident in cultures obtained from OA subjects and suggests a possible involvement of these cells in OA. Conclusions: Osteoclastogenic differentiation capability of PBMCs from OA subjects, also induced by B synoviocytes has been already documented. Here we hypothesized that SDSCs, generally considered for their regenerative potential in cartilage lesions, have also a role in the onset/maintenance of OA. Clinical relevance: Our observations may represent an interesting opportunity for the development of a holistic approach for OA treatment, that considers the multifaceted capability of MSCs in relation to the environment
Detecting senescent fate in mesenchymal stem cells: a combined cytofluorimetric and ultrastructural approach
No full textDetecting senescent fate in mesenchymal stem cells: a combined cytofluorimetric and ultrastructural approach
No full textSenescence can impair the therapeutic potential of stem cells. In this study, senescence-associated morphofunctional changes in periosteum-derived progenitor cells (PDPCs) from old and young individuals were investigated by combining cytofluorimetry, immunohistochemistry, and transmission electron microscopy. Cell cycle analysis demonstrated a large number of G0/G1 phase cells in PDPCs from old subjects and a progressive accumulation of G0/G1 cells during passaging in cultures from young subjects. Cytofluorimetry documented significant changes in light scattering parameters and closely correlated with the ultrastructural features, especially changes in mitochondrial shape and autophagy, which are consistent with the mitochondrial-lysosomal axis theory of ageing. The combined morphological, biofunctional, and ultrastructural approach enhanced the flow cytometric study of PDPC ageing. We speculate that impaired autophagy, documented in replicative senescent and old PDPCs, reflect a switch from quiescence to senescence. Its demonstration in a tissue with limited turnover—like the cambium layer of the periosteum, where reversible quiescence is the normal stem cell state throughout life—adds a new piece to the regenerative medicine jigsaw in an ageing society
Dental pulp stem cells senescence and regenerative potential relationship
No full textUncomplicated treatments for pulpitis and periodontitis continues to be challenging and regenerative approaches could meet this contingency. Dental pulp stem cells (DPSCs) represent a good candidate for oral recovering therapies. Here, we investigated changes in morphology, proliferation, and in vitro differentiation toward mesenchymal and neuronal phenotypes of human DPSCs harvested from differently aged donors. Aging is a physiologic phenomenon occurring with time that hamper body's capability to maintain homeostasis also affecting the functional reserve. Cytofluorimetric, immunohistochemical, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and western blot analyses were performed to gain insight for successful regenerative strategies in elderly. We observed a decline in DPSCs proliferation and differentiation potential with age. Interestingly, these cells behaved differently under osteogenic or odontogenic stimuli, showing different age-related mineralization capabilities. Similarly, neurogenic differentiation decreased with age. In conclusion, our observations represent a valid tool for the development of tailored regenerative strategies in an aging society
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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