Harnessing Endogenous Cellular Mechanisms for Bone Repair

Although autologous tissue transplantation represents a valid approach for bone repair, it has encountered crucial barriers in therapeutic translation, not least the invasive process necessary for stem cell isolation. In recent years, the scientific community has made significant strides for identifying new treatment options, and great emphasis has been placed on the tight interaction between skeletal and immune system in modulating the outcome of bone repair. Within the context of specific injury environmental cues, the cross talk among inflammatory cells and tissue resident and/or circulating progenitor cells is crucial to finely coordinate repair and remodeling processes. The appropriate modulation of the inflammatory response can now be considered a new trend in the field of regenerative medicine, as it raises the attracting possibility to enhance endogenous progenitor cell functions, finally leading to tissue repair. Therefore, new treatment options have been developed considering the wide spectrum of bone-inflammation interplay, considering in particular the cell intrinsic cues responsible for the modulation of the injured environment. In this review, we will provide a panoramic overview focusing on novel findings developed to uphold endogenous bone repair

La corruzione amministrativa: misure organizzative e semplificazioni per la prevenzione del fenomeno; profili nazionali, sovranazionali e internazionali

La corruzione è un fenomeno altamente insidioso che ostacola lo sviluppo economico, mina la democrazia e lede la giustizia sociale e lo Stato di diritto. Rispetto alle vicende degli anni Novanta - periodo nel quale la gravità del fenomeno ha suscitato livelli di allarme sociale analoghi a quelli odierni - si deve registrare nel nostro Paese un cambio di approccio nei tentativi di lotta alla corruzione. La sola repressione, affidata allo strumento sanzionatorio penale, non è parsa più sufficiente a contrastare un fenomeno > - che ha raggiunto, cioè, la sua massima espansione possibile - ma è emersa la necessità di strumenti di carattere preventivo. Questi ultimi si inseriscono all'interno di una strategia integrata e coordinata di contrasto - di cui alla L. n. 190 del 2012 (cd. legge anticorruzione) - basata non soltanto su misure repressive ma anche su misure amministrative, organizzative e strutturali, volte a combinare innovazione e semplificazione della P.A. con un rafforzamento a livello culturale ed etico del personale che compone l'apparato pubblico. Questo cambio di approccio va letto in concomitanza con l'emersione di una nozione di corruzione diversa e più ampia di quella penalistica: accanto alla corruzione come fattispecie di reato disciplinata dal Codice penale (artt. 318 e ss. c.p.) all'interno del Titolo dedicato ai "delitti contro la pubblica amministrazione", si tende a riconoscere l'esistenza di una nozione giuridicamente rilevante di corruzione che abbraccia un ventaglio ben più ampio di situazioni e comportamenti riconducibili non solo a fattispecie penalmente sanzionate ma anche a fatti apparentemente leciti e comunque riprovati dall'ordinamento giuridico. Vi rientrano fattispecie e relazioni giuridiche di vario genere, che a vario titolo si traducono in disfunzioni patologiche della pubblica amministrazione. A partire da tali premesse, la ricerca analizza la strategia amministrativistica di lotta al fenomeno ovvero le misure di semplificazione e i rimedi di carattere organizzativo messi in atto dal Legislatore in funzione di prevenzione e contrasto. Posto che qualsiasi settore d’intervento pubblico è vulnerabile alla corruzione, sono stati selezionati nell'analisi del fenomeno alcuni ambiti che per le loro caratteristiche sono maggiormente esposti a questo rischio (contratti pubblici, sanità, governo del territorio). L'ultima parte della ricerca è dedicata ai profili sovranazionali e internazionali di lotta alla corruzione, considerato che non si tratta di un problema limitato alla realtà locale-nazionale ma che trascende i confini dei singoli Stati e che, quindi, va combattuto attraverso strategie comuni a livello globale

33778 The impact and implications of COVID-19 on using scalp cooling therapy for prevention of chemotherapy-induced alopecia

Background: Scalp cooling therapy (SCT) is currently the most effective method to reduce chemotherapy-induced alopecia. Manual SCT requires a “capper” to change the caps throughout the infusion day whereas machine SCT only requires a 1-time cap fitting prior to infusion, usually performed by the health care staff. Coronavirus disease 2019 (COVID-19) brought restrictions on permitted infusion center visitors, which we hypothesized would include “cappers,” creating an additional barrier to SCT use. Methods: A scripted call was placed during May 2021 by a study author to infusion centers of Commission on Cancer (CoC) accredited hospitals in Michigan, New York City (NYC) and major cities in Texas in order to investigate how COVID-19 impacted SCT at their institution. The University of Michigan’s Institutional Review Board (IRB) deemed this study exempt from IRB approval. Results: Forty-one infusion centers were successfully contacted (40/62, 64.5%). Of the 33 that allow SCT, 41% (14) did not allow “cappers” under COVID-19 restrictions. Of the 13 institutions offering machine SCT, 92% (12/13) allowed patients to continue using the machines during the pandemic as it does not require an outside “capper.” Conclusion: Our study demonstrates the negative impact of COVID-19 on manual SCT use. As COVID-19 is likely here for the foreseeable future, it is critical to find ways to safely use SCT during these times. Hence, hospital adoption of SCT machines is even more critical given the pandemic, particularly for those of lower socioeconomic status and without strong social support

Learning from Mother Nature: Innovative Tools to Boost Endogenous Repair of Critical or Difficult-to-Heal Large Tissue Defects

For repair of chronic or difficult-to-heal tissue lesions and defects, major constraints exist to a broad application of cell therapy and tissue engineering approaches, i.e., transplantation of "ex vivo" expanded autologous stem/progenitor cells, alone or associated with carrier biomaterials. To enable a large number of patients to benefit, new strategies should be considered. One of the main goals of contemporary regenerative medicine is to develop new regenerative therapies, inspired from Mother Nature. In all injured tissues, when platelets are activated by tissue contact, their released factors promote innate immune cell migration to the wound site. Platelet-derived factors and factors secreted by migrating immune cells create an inflammatory microenvironment, in turn, causing the activation of angiogenesis and vasculogenesis processes. Eventually, repair or regeneration of the injured tissue occurs via paracrine signals activating, mobilizing or recruiting to the wound site cells with healing potential, such as stem cells, progenitors, or undifferentiated cells derived from the reprogramming of tissue differentiated cells. This review, largely based on our studies, discusses the identification of new tools, inspired by cellular and molecular mechanisms overseeing physiological tissue healing, that could reactivate dormant endogenous regeneration mechanisms lost during evolution and ontogenesis

Ankylosing Spondylitis and Mesenchymal Stromal/Stem Cell Therapy: A New Therapeutic Approach

Ankylosing spondylitis (AS) is an inflammatory rheumatoid disease categorized within spondyloarthropathies (SpA) and manifested by chronic spinal arthritis. Several innate and adaptive immune cells and secreted-mediators have been indicated to play a role in AS pathogenesis. Considering the limitations of current therapeutic approaches (NSAIDs, glucocorticoids, DMARDs and biologic drugs), finding new treatments with fewer side effects and high therapeutic potentials are required in AS. Mesenchymal stem cells (MSCs) with considerable immunomodulatory and regenerative properties could be able to attenuate the inflammatory responses and help tissue repair by cell-to-cell contact and secretion of soluble factors. Moreover, MSCs do not express HLA-DR, which renders them a favorable therapeutic choice for transplantation in immune-mediated disorders. In the present review, we describe immunopathogenesis and current treatments restrictions of AS. Afterwards, immunomodulatory properties and applications of MSCs in immune-mediated disorders, as well as recent findings of clinical trials involving mesenchymal stem cell therapy (MSCT) in ankylosing spondylitis, will be discussed in detail. Additional studies are required to investigate several features of MSCT such as cell origin, dosage, administration route and, specifically, the most suitable stage of disease for ideal intervention

Future Perspectives of Bone Tissue Engineering with Special Emphasis on Extracellular Vesicles

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