Applicability of bioengineered human skin: from preclinical skin humanized mouse models to clinical regenerative therapies

Ongoing progress in the field of regenerative medicine, in combination with the development of tissue-engineered skin products, has opened new possibilities for the treatment of certain diseases in which current treatments are aimed at alleviating symptoms but are not able to get a permanent cure. Our laboratory has developed a fibrin-based bioengineered human skin that has been successfully used for permanent regenerative therapies in different situations in the clinic. Moreover, we have been able to stably regenerate human skin by orthotopic grafting of this skin equivalent onto the back of immunodeficient mice. The so-called skin-humanized mouse model system has permitted us to model several monogenic skin diseases, when keratinocytes and fibroblasts harboring the genetic defect were used. In most cases different gene therapy approaches for ex vivo correction of cells have proved effective in reverting the phenotype using this model. More importantly, the feasibility of the system has allowed us to generate a skin humanized mouse model for psoriasis, a common chronic inflammatory disease where the immune component has a pivotal role in the pathogenesis. Establishing reliable humanized animal models for skin diseases is necessary to gain a deeper knowledge of the pathogenesis and to develop novel therapeutic strategies. In this sense, the skin humanized mouse model developed in our laboratory meets the needs of this field of research.This work was supported by grant SAF 2010-16976

Bularreko minbiziaren ondoren bizirautea lortu duten emakumeek dituzten beharren azterketa

56 p. -- Bibliogr.: p. 27-30Esparru kontzeptuala eta justifikazioa: Munduan bularreko minbizia diagnostikatzen zaien gero eta emakume gehiago badaude ere, denborarekin heriotza tasa asko jaisten ari da, minbizia honen bataz besteko biziraupena urtez-urte handituz. Tratamendua bukatu osteko etapa honetan dauden emakumeek lehen zeukaten sostengu askoz ere txikiagoarekin “normaltasun berriari” aurre egin behar diote, etapa honetako berezkoak diren erronkak kudeatzeko behar ugari azaleratzen dituztelarik. Gaur egun bularreko minbiziari aurre egin dioten emakumeak tratamenduaren osteko faseetan laguntzeko irizpide homogeneoak ezartzen dituzten jarraipen gidak dauden arren, hauek batez ere berreritzea ekiditera mugatzen dira, oraindik ez baitaude adostuta paziente hauen beharrak asetzeko gomendio amankomunak. Hortaz, jarraipen plan hauek osatu ahal izateko eta fase honetan dauden pazienteen bizi kalitatea hobetzeko, funtsezkoa ikusten da erizaintzaren aldetik emakumeen beharrak analizatzea. Helburua: Bularreko minbiziaren ondoren bizirautea lortu duten emakumeek dituzten beharrak aztertzea. Metodologia: Literaturaren errebisio kritikoa burutu da, hurrengo datu baseak kontsultatuz: Medline, Cinahl, PsycINFO, Cuiden, Cochrane, Embase, Lilacs. Halaber, eskuzko bilaketa ere burutu da aldizkari desberdinetan (Journal of Cancer Survivorship, European Journal of Cancer Care, European Journal of Oncology Nursing, Breast Cancer) eta ebidentzian oinarritutako baliabideetan (RNAO, NICE, JBI). Horrela, ezarritako barneratze irizpideak betetzen dituzten 16 artikulu eskuratu dira. Barneratze irizpide horien artean argitalpen data (2011-2021), hizkuntza (ingelesa edo gaztelera), artikulu mota (kuantitatibo, kualitatibo, literatura errebisioak, errebisio sistematikoak, metanalisiak, praktika klinikorako gidak), helburua (helburura egokitzen direnak), eskuragarritasuna (full-tex eran daudenak), populazioa (18 urtetik gorako emakumeak, biziraupen fase hedatu edo iraunkorrean daudenak), eta kultura edo geografia (munduko edozein lurraldean publikaturikoak) aurkitzen direlarik. Emaitzak eta eztabaida: Arlo desberdinetan dituzte beharrak emakumeek. Arlo fisikoan mina, nekea, linfedema, neuropatia periferikoa, pisu igoera eta funtzionaltasun galerarekin erlazionaturiko beharrak gaineztu dira; arlo psikosozialean, berreritzearen beldurra, antsietate, gorputz irudi, sexualitate, harreman aldaketa eta emozioen kudeaketarekin erlazionaturikoak; arlo ekonomikoan lanera bueltatzearekin eta finantziazio mugekin erlazionaturikoak; arlo espiritualean hazkuntza pertsonalarekin eta fedearekin erlazionaturikoak; eta arretaren arloan informazio eta koordinazioarekin erlazionaturikoak. Ondorioak eta inplikazioak: Emakumeek eta haien familia kideek arlo desberdinetan sostengua, laguntza, koordinazioa, baliabideak eta informazioa behar dituzte. Funtsezkoa da osasun profesionalek, hauen barnean erizainek, etapa honetan ematen diren erronkak ezagutzea, eta horiek artatzeko beharrezko gaitasunak eskuratzea, ondoren eguneroko praktikan emakumeei behar duten arreta eskaintzeko. Honetarako, garrantzizkoa da arlo honetan ikerketa egiten jarraitzea

Drug repurposing using biological networks

Drug repositioning is a strategy to identify new uses for existing, approved, or research drugs that are outside the scope of its original medical indication. Drug repurposing is based on the fact that one drug can act on multiple targets or that two diseases can have molecular similarities, among others. Currently, thanks to the rapid advancement of high-performance technologies, a massive amount of biological and biomedical data is being generated. This allows the use of computational methods and models based on biological networks to develop new possibilities for drug repurposing. Therefore, here, we provide an in-depth review of the main applications of drug repositioning that have been carried out using biological network models. The goal of this review is to show the usefulness of these computational methods to predict associations and to find candidate drugs for repositioning in new indications of certain diseases

Bioingeniería cutánea: aplicaciones preclínicas y clínicas

Regenerative Medicine is an emerging field that combines basic research and clinical observations in order to identify the elements required to replace damaged tissues and organs in vivo and to stimulate the body's intrinsic regenerative capacity. Great benefits are expected in this field as researchers take advantage of the potential regenerative properties of both embryonic and adult stem cells, and more recently, of induced pluripotent stem cells. Bioengineered skin emerged mainly in response to a critical need for early permanent coverage of extensive burns. Later this technology was also applied to the treatment of chronic ulcers. Our group has established a humanized mouse model of skin grafting that involves the use of bioengineered human skin in immunodeficient mice. This model is suitable for the study of physiologic and pathologic cutaneous processes and the evaluation of treatment strategies for skin diseases, including protocols for gene and cell therapy and tissue engineering.Our work has been funded by the Spanish Department of Science and Innovation (SAF2007-61019 and SAF 2010-16976), by the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), and by the Ministry of Health (Advanced Therapies Plan, TRA 0160)

Assessment of the risk and characterization of non-melanoma skin cancer in Kindler syndrome: study of a series of 91 patients.

BACKGROUND: Kindler Syndrome (KS) is a rare genodermatosis characterized by skin fragility, skin atrophy, premature aging and poikiloderma. It is caused by mutations in the FERMT1 gene, which encodes kindlin-1, a protein involved in integrin signalling and the formation of focal adhesions. Several reports have shown the presence of non-melanoma skin cancers in KS patients but a systematic study evaluating the risk of these tumors at different ages and their potential outcome has not yet been published. We have here addressed this condition in a retrospective study of 91 adult KS patients, characterizing frequency, metastatic potential and body distribution of squamous cell carcinoma (SCC) in these patients. SCC developed in 13 of the 91 patients. RESULTS: The youngest case arose in a 29-year-old patient; however, the cumulative risk of SCC increased to 66.7% in patients over 60 years of age. The highly aggressive nature of SCCs in KS was confirmed showing that 53.8% of the patients bearing SCCs develop metastatic disease. Our data also showed there are no specific mutations that correlate directly with the development of SCC; however, the mutational distribution along the gene appears to be different in patients bearing SCC from SCC-free patients. The body distribution of the tumor appearance was also unique and different from other bullous diseases, being concentrated in the hands and around the oral cavity, which are areas of high inflammation in this disease. CONCLUSIONS: This study characterizes SCCs in the largest series of KS patients reported so far, showing the high frequency and aggressiveness of these tumors. It also describes their particular body distribution and their relationship with mutations in the FERMT-1 gene. These data reinforce the need for close monitoring of premalignant or malignant lesions in KS patients

The RareDis corpus: A corpus annotated with rare diseases, their signs and symptoms

Rare diseases affect a small number of people compared to the general population. However, more than 6,000 different rare diseases exist and, in total, they affect more than 300 million people worldwide. Rare diseases share as part of their main problem, the delay in diagnosis and the sparse information available for researchers, clinicians, and patients. Finding a diagnostic can be a very long and frustrating experience for patients and their families. The average diagnostic delay is between 6–8 years. Many of these diseases result in different manifestations among patients, which hampers even more their detection and the correct treatment choice. Therefore, there is an urgent need to increase the scientific and medical knowledge about rare diseases. Natural Language Processing (NLP) can help to extract relevant information about rare diseases to facilitate their diagnosis and treatments, but most NLP techniques require manually annotated corpora. Therefore, our goal is to create a gold standard corpus annotated with rare diseases and their clinical manifestations. It could be used to train and test NLP approaches and the information extracted through NLP could enrich the knowledge of rare diseases, and thereby, help to reduce the diagnostic delay and improve the treatment of rare diseases. The paper describes the selection of 1,041 texts to be included in the corpus, the annotation process and the annotation guidelines. The entities (disease, rare disease, symptom, sign and anaphor) and the relationships (produces, is a, is acron, is synon, increases risk of, anaphora) were annotated. The RareDis corpus contains more than 5,000 rare diseases and almost 6,000 clinical manifestations are annotated. Moreover, the Inter Annotator Agreement evaluation shows a relatively high agreement (F1-measure equal to 83.5% under exact match criteria for the entities and equal to 81.3% for the relations). Based on these results, this corpus is of high quality, supposing a significant step for the field since there is a scarcity of available corpus annotated with rare diseases. This could open the door to further NLP applications, which would facilitate the diagnosis and treatment of these rare diseases and, therefore, would improve dramatically the quality of life of these patients.This work was supported by the Madrid Government (Comunidad de Madrid) under the Multiannual Agreement with UC3M in the line of "Fostering Young Doctors Research" (NLP4RARE-CM-UC3M) and in the context of the V PRICIT (Regional Programme of Research and Technological Innovation; the Multiannual Agreement with UC3M in the line of "Excellence of University Professors (EPUC3M17)"; and a grant from Spanish Ministry of Economy and Competitiveness (SAF2017-86810-R)

Sierra Nevada Global-Change Observatory. Monitoring methodologies

This book compiles detailed descriptions of the monitoring methodologies used for monitoring the global change impacts on ecosystems of Sierra Nevada

Humanization of tumor stroma by tissue engineering as a tool to improve squamous cell carcinoma xenograft

The role of stroma is fundamental in the development and behavior of epithelial tumors. In this regard, limited growth of squamous cell carcinomas (SCC) or cell-lines derived from them has been achieved in immunodeficient mice. Moreover, lack of faithful recapitulation of the original human neoplasia complexity is often observed in xenografted tumors. Here, we used tissue engineering techniques to recreate a humanized tumor stroma for SCCs grafted in host mice, by combining CAF (cancer associated fibroblasts)-like cells with a biocompatible scaffold. The stroma was either co-injected with epithelial cell lines derived from aggressive SCC or implanted 15 days before the injection of the tumoral cells, to allow its vascularization and maturation. None of the mice injected with the cell lines without stroma were able to develop a SCC. In contrast, tumors were able to grow when SCC cells were injected into previously established humanized stroma. Histologically, all of the regenerated tumors were moderately differentiated SCC with a well-developed stroma, resembling that found in the original human neoplasm. Persistence of human stromal cells was also confirmed by immunohistochemistry. In summary, we provide a proof of concept that humanized tumor stroma, generated by tissue engineering, can facilitate the development of epithelial tumors in immunodeficient miceThis research was funded in part by SCIENCE AND INNOVATION MINISTRY OF SPAIN; grant number [SAF2017-86810-R], INSTITUTO DE SALUD CARLOS III [PI17/01747], both co-funded with European Regional Development Funds (ERDF). Additional funds come from COMUNIDAD DE MADRID [B2017/BMD-3692], and DEBRA International. AGM was supported by a research scholarship of the ASOCIACIÓN ESPAÑOLA CONTRA EL CANCER (AECC), Spain

Sinfonevada: Dataset of Floristic diversity in Sierra Nevada forests (SE Spain)

The Sinfonevada database is a forest inventory that contains information on the forest ecosystem in the Sierra Nevada mountains (SE Spain). The Sinfonevada dataset contains more than 7,500 occurrence records belonging to 270 taxa (24 of these threatened) from floristic inventories of the Sinfonevada Forest inventory. Expert field workers collected the information. The whole dataset underwent a quality control by botanists with broad expertise in Sierra Nevada flora. This floristic inventory was created to gather useful information for the proper management of Pinus plantations in Sierra Nevada. This is the only dataset that shows a comprehensive view of the forest flora in Sierra Nevada. This is the reason why it is being used to assess the biodiversity in the very dense pine plantations on this massif. With this dataset, managers have improved their ability to decide where to apply forest treatments in order to avoid biodiversity loss. The dataset forms part of the Sierra Nevada Global Change Observatory (OBSNEV), a long-term research project designed to compile socio-ecological information on the major ecosystem types in order to identify the impacts of global change in this area.All the information contained in Sinfonevada was gathered by TRAGSA (Transformación Agraria S.A.), a public company funded by the Spanish Ministry of the Environment. The Sierra Nevada Global Change Observatory is funded by the Andalusian Regional Government (via Environmental Protection Agency) and by the Spanish Government (via “Fundación Biodiversidad”, which is a Public Foundation)