Regenerative medicine for an ageing population: are we there yet?

Una de les conseqüències de l’augment en l’esperança de vida de la societat actual és l’envelliment de les cèl·lules i els teixits que conformen el nostre organisme. Mantenir o recuperar la funcionalitat perduda de teixits i òrgans en edats avançades és un repte per a la medicina. La medicina regenerativa és una disciplina que estudia noves teràpies personalitzades mitjançant l’ús de gens, cèl·lules i teixits com a parts integrants dels medicaments. Malgrat la promesa que aquests nous medicaments permetran mantenir o restituir l’arquitectura i funció d’òrgans i teixits danyats o degenerats per malalties i l’edat, a dia d’avui, pocs productes de medicina regenerativa han estat autoritzats per al seu ús clínic i els pocs que ho són, no es troben disponibles arreu ni són accessibles a tothom. En aquest treball, es presenten conceptes bàsics de la medicina regenerativa i s’avalua el seu impacte en la millora de la qualitat de vida d’una població envellida.A consequence of the increase in life expectancy of our population is the gradual ageing of cells and tissues in our bodies, which does not necessarily match the pace of approval of new developments in medicine that would allow for the maintenance or recovery of tissue and organ functionality. Regenerative medicine is a growing field that aims to alter the current practice of medicine by treating the root causes of diseases and disorders using personalized therapeutic approaches that employ genes, cells and tissues as integral parts of the new medicines. Despite high expectations that regenerative medicine will restore the architecture of damaged or aged organs and tissues, few products have been marketed so far, and not all of them are readily available everywhere or to everyone. This article presents a review of the concepts of regenerative medicine and assesses the extent to which it can improve the quality of life of an ageing population

La música, una eina per a la globalització a pàrvuls de 5 anys.

«És costum proposar als infants… cantarelles, imitacions, jocs… contes, etc., activitats que estimulen i reforcen l’acció mediatitzada del pensament de l’infant i les relacions de transacció amb l’altre» (Departament d’Ensenyament, pàg. 11). Basant-nos en aquesta idea, i aprofitant el valor motivador de la cançó, va sorgir la idea d’elaborar un material inèdit que, partint d’una cançó la lletra de la qual repeteix un determinat fonema, ens permetés globalitzar les activitats de diferents àrees, de manera que els nens i les nenes de Parvulari 5 anys, als quals va dirigit, poguessin copsar i interioritzar els conceptes que ens proposem

La Plana Justa (Xàbia, Alicante): un nuevo yacimiento con materiales fenicios y del ibérico antiguo

Presentamos el yacimiento protohistórico de la Plana Justa, localizado en el curso de las prospecciones realizadas en los últimos años por el Museu Arqueològic i Etnogràfic Municipal “Soler Blasco” de Xàbia (Alicante). Los restos que se observan en superficie son algunos basamentos de muros y cerámicas –además de otros materiales– que podemos datar entre los ss. VII-V a.C. en base a sus características tecnológicas y a las importaciones presentes, por lo que el asentamiento ofrece buenas perspectivas para el estudio de los períodos más antiguos de la Edad del Hierro. De momentos posteriores son algunas cerámicas de cronología andalusí (ss. X-XI?), indicadoras de una ocupación de escasa entidad que parece situarse en la zona más alta del área que nos ocupa

Protecció del procés de mort cel·lular programada en cultius in vitro de cèl·lules animals

Consultable des del TDXTítol obtingut de la portada digitalitzadaDavant la impossibilitat econòmica i física de controlar enginyerilment tots els paràmetres involucrats en la pèrdua de viabilitat en cultius in vitro de cèl·lules animals quan es dóna una limitació en el subministrament de nutrients, així com per la presència d'elevades concentracions de subproductes tòxics del metabolisme, en aquest treball s'ha explorat la modificació tant de la formulació del medi com genètica de cèl·lules d'hibridoma amb l'objectiu de perllongar la seva supervivència dins els bioreactors i rendibilitzar el procés d'obtenció d'anticossos monoclonals. La reformulació del medi va permetre alentir la proliferació cel·lular i retardar l'exhauriment de nutrients essencials. Tanmateix, aquests canvis induïen la mort cel·lular per apoptosi. El bloqueig de l'apoptosi mitjançant l'ús d'inhibidors peptídics específics de Caspases va permetre no només retardar la pèrdua de viabilitat dels cultius si no també recuperar-los 36 hores després d'haver induït la mort per manca de glutamina. Resultats similars es van obtenir en la inhibició genètica de l'activació de les Caspases sobreexpressant gens protectors de la família de Bcl-2, tant d'origen endogen com víric. A més a més, els cultius d'aquestes noves línies cel·lulars d'hibridoma poden ser recuperats després d'haver estat sotmesos fins a 48 hores sota condicions inductores de l'apoptosi. Aquests resultats demostren la viabilitat d'incorporar una vàlvula de seguretat genètica que permet retardar el procés de mort per apoptosi de cèl·lules que, en altres circumstàncies, moririen i s'acumularien en el bioreactor. A més a més, la sobreexpressió de gens antiapoptòtics fa les cèl·lules més resistents i permet recuperar cultius que, per causes accidentals inherents a la metodologia emprada en el monitoratge i control del bioprocés o per limitacions físiques de subministrament de nutrients, factors de creixement i oxigen, es vegin sotmeses a condicions inductores de l'apoptosi. D'aquesta manera, aquest treball de tesi contribueix a la creació d'un sistema de cultiu més robust que evitaria l'enorme pèrdua de rendibilitat en els processos d'obtenció del producte desitjat quan els cultius entren en la fase de mort per apoptosiDue to the economical and physical unavailability to control a number of parameters involved in the loss of viability of animal cell cultures as a result of a limitation in nutrient supply, as well as high levels of toxic byproducts, we have explored the effect of medium modification on cell viability as well as the genetic manipulation of hybridoma cells with the aim of prolonging the life span of these cultures in bioreactors and therefore optimize the productivity of monoclonal antibodies. Reformulation of culture medium allowed a decrease in cellular proliferation and therefore delay nutrient exhaustion. However, these changes induce cell death by apoptosis. The use of caspase inhibitors has enabled to mantain cell viability during a significant period of time, when glutamine depletion was maintained in the culture. Two caspase inhibitors partially suppressed the progress of PCD under glutamine deprivation: Ac-DEVD-cho and z-VAD-fmk. Indeed, as a consequence of this protection, the number of viable cells decreased by 10% (for z-VAD-fmk) and by 80% (for Ac-DEVD-cmk) after 36 hours of culture, while it decreased by 90% for a control culture in absence of protective compounds. However, when the culture was exposed to non-apoptotic conditions after this period of time under apoptosis protection conditions, normal growth pattern was not recovered. Interestingly, the simultaneous use of both inhibitors made the recovery of the cell culture possible even after a period of 36 hours under glutamine depletion, indicating that the inhibition of the effector caspases occurs upstream of the point in which hybridoma cells enter into the commitment step of the death programme. Similar results were obtained by genetic inhibition of the Caspase cascade activation by means of overexpression of protector genes of the Bcl-2 family: Bcl-2, Bcl-XL, and viral homolgues BHRF-1 and KSBcl-2. Moreover, cultures of these genetically modified hybridomas could be rescued from cell death phase after a significant period of time (i.e., 24 and 48 h) under apoptosis inducing conditions. These results show the viability of the incorporation of a security valve that could delay the cell death process by apoptosis in cell cultures which, under other circumstances, would die and be accumulated in the bioreactor. Moreover, overexpression of Bcl-2 homologues make hybridomas more resistant to apoptosis and allow the recovery of viability of cultures deprived from glutamine after 48 hours of apoptosis inducing conditions. Thus, the present work help towards the creation of a more robust culture system that will avoid tremendous loss of cost-effectiveness of biotechnological processes when cultures of animal cells trigger apoptosis

The Quality Management Ecosystem in Cell Therapy in Catalonia (Spain): An Opportunity for Integrating Standards and Streamlining Quality Compliance

Integrated management system; Quality compliance; Quality standardsSistema de gestión integrado; Cumplimiento de la calidad; Estándares de calidadSistema de gestió integrat; Compliment de la qualitat; Estàndards de qualitatCell therapies are required to meet with compulsory regulations that co-exist with other optional standards and guidelines that together compose a complex quality management system. Indeed, reliable insights on the mechanisms of action and safety of novel cell-based therapies require adherence to solid quality management structures in all steps of the value chain, from early research and tissue procurement to clinical trials and biovigilance, thus guaranteeing reproducibility and solid foundations for better science and improved clinical practice. Herein we present the concept of the quality ecosystem as a tool to understand and assist all stakeholders involved in developing and structuring the integration of standards as novel developments are taking place. We conclude that the various quality management initiatives can all be thought about under the umbrella of an ecosystem.Work in JV’s laboratory is supported by the Spanish Advanced Therapy Network (TERAV, expedient No. RD21/0017/0022), awarded by the Generalitat de Catalunya as Consolidated Research Group (ref. 2017SGR719) and funded by Ministerio de Ciencia Innovación y Universidades de España (Instituto de Salud Carlos III, expedient No. PI19/01788)

Development of a self-reporting tool to obtain a Combined Index of Severity of Fibromyalgia (ICAF*)

<p>Abstract</p> <p>Background</p> <p>Fibromyalgia is a syndrome with heterogeneous symptoms. The evaluation in the clinical setting usually fails to cover the complexity of the syndrome. This study aims to determine how different aspects of fibromyalgia are inter-related when measured by means of a self-reporting tool. The objective is to develop a more complete evaluation model adjusted to the complexity and multi-dimensional nature of the syndrome.</p> <p>Methods</p> <p>Application was made of the Fibromyalgia Impact Questionnaire, the Hospital Anxiety and Depression Scale, the Brief Pain Inventory, the Fatigue Assessment Scale, the Health Assessment Questionnaire, the General Health Questionnaire (GHQ-28), the Chronic Pain Coping Inventory, the Arthritis Self-efficacy Scale and the Sleep Quality Scale. An assessment was made, on the basis of clinical interviews, case histories and specific tests, of the patient sociodemographic data, comorbidity, physical exploration and other clinical indexes. An exploratory factor analysis was made, with comparisons of the clinical index scores in extreme groups of patients.</p> <p>Results</p> <p>The ICAF composed of 59 items was obtained, offering four factors that explain 64% of the variance, and referred to as Emotional Factor (33.7%), Physical-Activity (15%), Active Coping (9%) and Passive Coping (6.3%). A t-test between the extreme scores of these factors in the 301 patients revealed statistically significant differences in occupational status, medically unexplained syndromes, number of tender points, the six-minutes walk test, comorbidity and health care costs.</p> <p>Conclusions</p> <p>This study offers a tool allowing more complete and rapid evaluation of patients with fibromyalgia. The test intrinsically evaluates the emotional aspects: anxiety and depression, and their impact upon social aspects. It also evaluates patient functional capacity, fatigue, sleep quality, pain, and the way in which the patient copes with the disease. This is achieved by means of a self-assessment questionnaire based on elements from well known tests.</p

Cell and gene therapy workforce development: the role of the International Society for Cell & Gene Therapy (ISCT) in the creation of a sustainable and skilled workforce in Europe

Advanced therapy medicinal products; Career development; TrainingMedicamentos de terapia avanzada; Desarrollo profesional; FormaciónMedicaments de teràpia avançada; Desenvolupament professional; FormacióThe development and production of cell gene and tissue (CGT)-based therapies requires a specialized workforce. Entering the CGT arena is complex because it involves different scientific and biomedical aspects (e.g., immunology, stem cell biology and transplantation), as well as knowledge of regulatory affairs and compliance with pharmaceutical quality standards. Currently, both industry and academia are facing a worldwide workforce shortage, whereas only a handful of educational and training initiatives specifically address the peculiarities of CGT product development, the procurement of substances of human origin, the manufacturing process itself and clinical monitoring and biovigilance. The training offered by traditional Master's and PhD programs is not suited for training a skilled workforce ready to enter the increasingly fast-growing CGT field. Indeed, typically these programs are of long duration and only partially cover the required competencies, whereas the demand for a specialized workforce relentlessly increases. In this paper, we (i) present and discuss our understanding of the roots of current growth acceleration of the CGT field; (ii) anticipate future workforce needs due to the expected increase of marketed CGT-based therapies and (iii) evaluate potential solutions that seek to adapt, develop and implement current educational and training initiatives. Importantly for these solutions, we call for scientific societies, such as the International Society for Cell & Gene Therapy, to play a more active role and act as catalysers for new initiatives, building bridges between academia and Industry to establish effective educational and training programs that will engage and prepare a new generation of qualified professionals for entry into the CGT field

Rmst Is a Novel Marker for the Mouse Ventral Mesencephalic Floor Plate and the Anterior Dorsal Midline Cells

The availability of specific markers expressed in different regions of the developing nervous system provides a useful tool to illuminate their development, regulation and function. We have identified by expression profiling a putative non-coding RNA, Rmst, that exhibits prominent expression in the midbrain floor plate region, the isthmus and the roof plate of the anterior neural tube. At the developmental stage when the ventral dopaminergic neuron territory is being established, Rmst expression appears to be restricted to the presumptive dopaminergic neurons of the ventral tegmental area that lies close to the ventral midline. Thus this study presents Rmst as a novel marker for the developing dopaminergic neurons in the mesencephalic floor plate as well as a marker for the dorsal midline cells of the anterior neural tube and the isthmic organizer