Author Archives: Biodonostia

Biodonostia leads the research to reduce the time taken to make treatment decisions for lung cancer patients

Marek Grzelczak, Charles Lawrie y Sergio Arana

The Molecular Oncology Group of Biodonostia Health Research Institute (HRI) has been leading a project INDICATE (IN vitro DIagnostic CAncer TEst) that aims to develop a simple, economical and rapid test to detect clinically relevant cancer-associated mutations in the blood of patients in a point-of-care (POC) format similar to the pregnancy test.

The objective of the project is to reduce the time taken to make treatment decisions for lung cancer patients which currently can take up to one month between testing and treatment prescription. This delay can cause great distress to the patient and their families, increased costs and can reduce the effectiveness of treatment. The test aims to reduce testing time to less than an hour allowing treatment decisions to be taken within the same hospital appointment.

The technology behind the test is based on a combination of nanoparticles and polymers in a hybrid microfluidic and lateral flow device. This multi-disciplinary project was initiated as a collaboration between Biodonostia HRI and CIC biomaGUNE that was later expanded to include researchers from Polymat and UPV, and more recently researchers from DIPC and CEIT. The project has been funded over the last few years with the generous support of ISCIII and the GV- Department of Health and led to several high impact publications in scientific journals and an approved European-wide patent to protect the technology (also filed in the US, Japan and China). The project has also led to the creation of a spin-off company Indicate Solutions that was formed to exploit and commercialise the technology.

The project is led by Prof. Charles Lawrie, head of the Onocology Research Area of IIS Biodonostia who also serves as the acting CEO of Indicate Solutions. Together with Professor Lawrie participate in the project, among others, Sergio Arana, Chief researcher of Ceit-IK4, Dr. Marek Grzelczak, Chief researcher of THE DIPC and Prof. Luis Liz-Marzan, scientific director of CIC Biomagune. Also involved in the Project are clinicians from HUD, HUC and HUA who will coordinate patient identification and sample collection and provide clinical overview to the project.

Click here to see the recent interview with the researches in El Confidencial (Spanish)

Researchers at Biodonostia discover that four inner cell contacts drive the mouse embryo from totipotency to pluripotency

A non-cell autonomous mechanism, based on a minimal number of four inner-cell contacts in the Inner Cell Mass (ICM) of the mouse embryo at E(mbryonic day)3.25 activates the pluripotency master regulator Oct4 and establishes in vivo a very early naïve pluripotent state.

Research, led by Dr. Marcos J. Araúzo Bravo from the Computational Biology and Systems Biomedicine Research Group of the IIS Biodonostia, has just been published online in the open access journal Scientific Reports, belonging to the prestigious publication group Nature, in an article whose first author is Dr. Daniela Gerovska.

The article revisits the study of the 32- to 64-cell mouse embryo transition during the embryonic day E3.25, associated traditionally in literature with the search for an early onset of the second cell-fate decision, the specification of the Inner Cell Mass (ICM) to primitive endoderm and epiblast.

The objective has been to discover new events of very early embryonic decisions that have remained elusive till now for the traditional techniques. For this purpose, the authors designed a new clustering algorithm: Hierarchical Optimal k-Means clustering (HOkM), and applied it on single-cell microarray transcriptomics data from E3.25.

Thanks to this new algorithm they discovered two new subpopulations of ICM cells: the subpopulation from embryos with less than 34 cells (E3.25-LNCs), and the subpopulation from embryos with more than 33 cells (E3.25-HNCs), corresponding to two different developmental stages.

Analyzing the differently expressed genes between the E3.25-LNCs and E3.25-HNCs subpopulations, they found that the expression of Oct4, pluripotency master regulator, is unstable in the subpopulation E3.25-LNC, and stabilizes at high level in the E3.25-HNC subpopulation, with Basigin highly expressed and the chromatin remodeling program initialized to establish a very early naïve pluripotent state in the E3.25-HNCs. The authors hypothesized the existence of a non-cell autonomous mechanism, based on the requirement for at least four inner-cell contacts in a 6-cell kernel in the ICM of embryos with more than 33 cells, which activates Oct4 in the mouse preimplantation embryo.

Computational analysis of single-cell transcriptomics data elucidates the stabilization of Oct4 expression in the E3.25 mouse preimplantation embryo. Daniela Gerovska & Marcos J. Araúzo-Bravo. Scientific Reports.

The paper is freely available online at: www.nature.com/articles/s41598-019-45438-y

 

Biodonostia hosts the EATRIS-Spain conference on Translational Medicine and Research

The conference included presentation of the European infrastructure for translational medicine, EATRIS, which enables fast and personalised access to state-of-the-art technologies, bringing them closer to patients

On May 3, the Biodonostia HRI headquarters hosted a meeting of the members of EATRIS Spain, with the participation of 15 of its accredited health research institutes, among them Osakidetza’s Biodonostia HRI, the aggregate value of which is the creation of knowledge in the field of health research. This knowledge comes from the first-hand clinical experience in outstanding hospitals, which constitute the perfect environment for the expedition of biomedical knowledge to clinical practice and, therefore, to the patient (and vice versa). The conference included the presentation of EATRIS, the European infrastructure for translational medicine, which enables fast and personalised access to state-of-the-art technologies, bringing them closer to patients. The Spanish node of EATRIS falls beneath the umbrella and coordination of the Carlos III National Health Institute (ISCIII), as mandatory official representative of Spain in EATRIS, and the Vall d’Hebron Research Institute (VHIR) as scientific leader. This initiative allows the use at European level of large scientific infrastructures, as well as the connecting of research groups with common questions, bringing the companies (and their questions) closer to the research groups (who can help with the answers). Translational research is the kind that focusses on patient benefit. One example of this would be the study of a molecule in the laboratory and which in its progression ends up becoming a medicine for treatment of the disease being studied. One important challenge in the development of innovations in this kind of research is understanding what steps must be taken and what experience and technologies are adequate for taking these steps. Hence the presentation of EATRIS at this conference, with the objective that the interested Institutes may participate in this European infrastructure, and in the clinical, biological and technological experience available within it, in benefit of translational research. In order to discuss these questions, the conference had the participation of speakers of extensive background and prestige in relevant bodies, such as Dr Raquel Yotti (Director of the Carlos III Health Institute, ISCII); Dr Antoni Andreu (Scientific Director of EATRIS), Dr Joan Comella (Director of the VHIR and Scientific Coordinator of EATRIS-Spain); and Anton Ussi (Director of Operations and Finances at EATRIS).

 

Biodonostia presents its advances on the Strategy of Research on Aging

On April 4, at Biodonostia, a presentation was made of the Strategy of Research on Aging developed by the Institute, focussed on presenting the lines of research which have gradually emerged, as well as the results of several studies carried out in the last five years.

The event, which was opened by the Director of the Institute, Dr Julio Arrizabalaga, had the participation of all of the researchers in the different groups involved in the research, headed by their coordinators, Dr Ander Mateu and Dr Itziar Vergara, wo presented the progress achieved in their specific fields.

Several questions were discussed during the event, such as the environmental and biological factors of healthy human aging and those which provoke premature aging; the epidemiological, social and economic implications of aging and associated illnesses; the biological determinants responsible for aging and identification of their common physiopathological substrate, and the determinants of active and health aging and fragility.

Healthy aging represents a socioeconomic challenge of enormous magnitude in advanced societies, where the aging population is constantly on the rise, generating important imbalances in health care and in the sustainability of a universal health care system. Thus, the Basque Statistics Office, Eustat, in its document «Projections of the population of Gipuzkoa 1995-2020», anticipates a seriously imbalanced global population census, given that the number will be much lower at the base of the pyramid, while the oldest group (>65) will rise notably, attaining a relative weight of 24% in the overall population in 2020.

Conscious of this reality, in 2013 the Biodonostia HRI proposed an R&D&I strategy focussed on aging, to which it designated the acronym IKAGURE-BD, and in which an endeavour has been made to incorporate the different actors of its environment who work in the field of Health.

Researchers at Biodonostia develop a kit to detect and identify variants of one of the main agents responsible for respiratory infections

The agent is associated to benign infections such as acute otitis media and sinusitis, as well as to severe infections such as bacteraemia, meningitis and pneumonia.

Researchers from the Respiratory Infection and Antimicrobial Resistance Group of Osakidetza’s Biodonostia Health Research Institute (HRI)-Donostialdea IHO have developed this test enabling the identification of 76 different S. pneumoniae serotypes in DNA samples taken from bacterial cultures.

S.pneumoniae is responsible for high morbidity and mortality, being one of the principle causal agents of a wide variety of clinical conditions, from benign infections such as acute otitis media and sinusitis, to severe infections such as bacteraemia, meningitis and pneumonia.

This is a major advance, given that infections due to S. pneumoniae represent an important Public Health problem both in industrialised and in less developed countries.

Licencing the kit has been possible thanks to the Biodonostia HRI Research Support unit, a relevant node of the ITEMAS Network, which has coordinated the project between the research group and validations at the Donostialdea IHO Microbiology Department as well as managing the Research Results Transfer Office (OTRI) belonging to the Basque Foundation for Health Innovation and Research (BIOEF), a support structure in the Basque innovation process and also an important ITEMAS node.

PneumoStrip is a test enabling the detection and identification in DNA samples, taken from microbial cultures, of 76 S. pneumoniae serotypes. Until now, more than 95 different types (serotypes) of pneumococcus have been described, which are differentiated by the composition of their external capsule. Currently vaccines are available for a limited number (13 or 23) of these serotypes, according to the data handled by Txema Marimón, Head of the Respiratory Infection and Antimicrobial Resistance Group at the Biodonostia HRI, and one of the four creators of the kit.

An explanatory video can be found below:

Researchers at Biodonostia and Ibima identify a method to obtain stem cells from human muscle

Using these cells represents advantages for cell therapy in patients suffering from urinary or anal incontinence with sphincter muscle damage, or for treating small-sized muscle groups, such as in the case of oculopharyngeal muscular dystrophy or facioscapulohumeral dystrophy. .

Researchers at the Biodonostia Health Research Institute (Biodonostia HRI) dedicated to regenerative medicine and cell therapy in the scope of muscular regeneration, have patented and published a method for the isolation and expansion of multipotent stem cells obtained from the cremaster muscle.

La investigación, liderada por los Dres. Ander Izeta y Adolfo López de Munáin, de los Grupos de Ingeniería Tisular y Enfermedades Neuromusculares del IIS Biodonostia, en colaboración con investigadores del Instituto de Investigación Biomédica de Málaga (IBIMA), IIS Aragón de Zaragoza y del centro tecnológico Idonial de Gijón, acaba de publicarse online en la revista de acceso abierto Scientific Reports, perteneciente al prestigioso grupo de publicaciones Nature, en un artículo cuya primera autora es la Dra. Neia Naldaiz-Gastesi.

The patent, which protects the method for obtaining these cells and their therapeutic uses, was submitted in March 2018 to the Spanish Patent and Trademark Office and has recently earned the qualification of international patent in the member countries of the Patent Cooperation Treaty (PCT).

The inventors suggest that the use of multipotent precursor cells (myogenic, vascular and neural) isolated from the cremaster muscle of adult males presents advantages for cell therapy in patients suffering from urinary or anal incontinence with sphincter muscle damage, or for treating small-sized muscle groups, such as in the case of oculopharyngeal muscular dystrophy or facioscapulohumeral dystrophy.

The above-mentioned research consortium is currently working on using these cells in a tissue engineering product made by means of 3D bioprinting to treat stress incontinence, a widely prevailing pathology in our society and whose diagnosis is believed to be vastly underestimated, as well as on the isolation of a similar population of precursor cells from the muscles of adult women.

Reference:

Isolation and characterization of myogenic precursor cells from human cremaster muscle
Neia Naldaiz-Gastesi, María Goicoechea, Isabel M-ª Aragón, Virginia Pérez-López, Sandra Fuertes-Alvarez, Bernardo Herrera-Imbroda, Adolfo López de Munain, Resi de Luna-Diaz, Pedro M. Baptista, M. Alejandro Fernández, María Fernanda Lara & Ander Izeta.

 

Over 60% of Hearing Deficits in Newborns Are of Genetic Origin

Recently, was presented an international study for the early diagnosis of hipoacusias by means of genomic tools (GHELP project), led by the University of Navarra Clinic, in which 8 other centres from Spain, Portugal and France participate, including the IIS Biodonostia.

Five out of every thousand children are born with some type of hearing deficiency in south-western Europe. Thus, the GHELP project has the aim of improving the current programmes for the early detection of hearing deficits. Led by the Clínica Universidad de Navarra, this is an international genetic study for the diagnosis of hearing disorders in new-borns. The GHELP project is co-financed by the Interreg Sudoe Program through the European Regional Development Fund (ERDF).

“Early detection improves the speech and language skills of children with hearing loss. It has been shown that intervention before the age of 12 months yields significantly better results than  a later intervention,” explained Dr. Manuel Manrique, Project Coordinator and Director of the Otorhinolaryngology Department of the Clinic.

The basis of this study is the GHELP panel, a genomic diagnostic tool that analyses the most important genes involved in hearing loss. Genetic factors are one of the main causes of this disease, as it is estimated that 60-70% of cases of hearing loss among children are of genetic origin.

The usual screening programs for early diagnosis in new-borns will be used for this panel, together with samples from both the Clinic’s patients and those of five other centres located in Spain, Portugal, and France.

This was explained by Dr. Manuel Manrique at the project’s public presentation, where he was accompanied by Dr. Gorka Alkorta of the Genomics Unit of the University of Navarra’s CIMA LABX, and Dr. Ana Patiño, Director of the Clinical Genetics Unit of the Clinic, as members of the research team.

The event was also attended by José Andrés Gómez Cantero, Director of the Clinic, and Javier Mata Rodríguez, Director of the Research Management Service of the Universidad de Navarra. In addition, the benefits of this project for Health Administrations and individuals with hearing loss was analysed by Dr. Nieves Ascunce, Head of the Epidemiology and Health Prevention Service, and Dr. Maria Ederra, Head of the Early Detection Unit, both from the Institute of Public and Occupational Health of Navarra (Spain).

The results of the study will allow for reaching the specific diagnosis of the patient and predict their potential prognosis.

In addition, the project aims to achieve three other objectives: to gain a better understanding of the genetic mutations involved in hearing deficits in new-borns, including a genetic study as a regularly applied tool to obtain more sensitive and specific results, and establishing a platform that will allow other centres to take advantage of this technology.

The Centres participating in the project are: Clínica Universidad de Navarra (coordinator), Instituto de Salud Pública y Laboral de Navarra (Institute of Public and Occupational Health of Navarra), Asociación Instituto Biodonostia, DREAMgenics S.L., Hospital CUF Porto S.A., Centro Hospitalar Lisboa Central, EPE, Centre Hospitalier Universitaire de Montpellier, and the Centre Hospitalier Universitaire de Toulouse.

More information

Biodonostia researcher Jesús Bañales co-heads a European Horizon 2020 project addressing 3 types of liver cancer

The research project is part of the European Research and Innovation Programme Horizon 2020, one of the most competitive and prestigious at international level, and is funded with €3.5 million.

An international consortium co-headed by Dr Jesús Bañales, Head of the Hepatic Diseases Group at Osakidetza’s Biodonostia Health Research Institute (Biodonostia HRI), has obtained €3.5 million for a study of liver cancer (hepatocellular cancer), bile duct cancer (cholangiocarcinoma) and gallbladder cancer, in the framework of the European Research and Innovation Programme Horizon 2020. Together with Drs André Boonstra and José Debes (Erasmus Medical Center, Rotterdam, the Netherlands), who will act as coordinators, and Dr Juan Carlos Roa (Catholic University of Chile, Santiago, Chile), Dr Bañales heads a collaboration between Europe and South America to determine new risk factors and non-invasive early diagnosis markers for these hepatobiliary cancers.

These tumours represent one of the main causes of death worldwide and are exceptionally aggressive in Latin America, largely affecting relatively young people.

Outstanding among the high death rate of these tumours is the lack of non-invasive, sensitive and specific early detection methods, since those currently in use are complex, requiring advanced imaging technologies and tumour biopsy studies. This problem is significantly worse in regions with limited resources, meaning that these tumours are generally diagnosed at advanced stages and with very poor prognosis. In the words of Dr Bañales: “To overcome these barriers, we have proposed the validation of biomarkers (inflammatory, proteomic profiling of extracellular vesicles, and circulating tumour DNA) present in blood and recently described by our research group, thereby enabling us to determine their clinical use for the non-invasive and specific diagnosis of these tumours. On the other hand, we want to increase the knowledge of potential risk factors (genetic, infectious) associated to the development of these tumours”. Within this project, a comparison will be made between the situation in Europe and that of Latin America. The project will therefore have partners from five Latin American countries (Argentina, Brazil, Colombia, Chile and Ecuador), four EU countries (Germany, Spain, the Netherlands, the United Kingdom) and Canada. 

Over the next 4 years, the Biodonostia HRI Hepatic Diseases Group headed by Dr Bañales will lead one of the 3 scientific programmes, on cholangiocarcinoma, and will actively participate in the other two (on hepatocellular carcinoma and gallbladder cancer). Other participants in the project will be Drs Luis Bujanda (Head of the Hepatic and Gastrointestinal Diseases Area at the Biodonostia HRI) and Raúl Jimenez, Adelaida Lacasta, Maria Jesús Perugorría, Pedro Rodrigues and Elizabeth Hijona from the Biodonostia HRI and the Donostia University Hospital (DUH).

Dr Bañales is an Ikerbasque, Miguel Servet and CIBERehd researcher, as well as Associate Professor at the Mayo Clinic (USA), University of Navarra (Spain) and Universidad Area Andina (Colombia). He is also co-founder and coordinator of the European Network for the Study of Cholangiocarcinoma (ENSCCA), as well as coordinator of a European database of patients with cholangiocarcinoma, containing more than 2000 cases.

 

First steps of the Multidisciplinary Unit to develop Bio-Models, Bio-Inks and 3D Bio-Printing at Biodonostia

Development of the 3D printing area is currently one of the main strategic R&D&I endeavours at the Biodonostia HRI.

A patient-specific 3D printed model of a tumor in the chest wall

In line with the situation at other health research institutes and hospitals, the Biodonostia HRI has decided to promote a Multidisciplinary Unit on Bio-models, Bio-inks and 3D Bioprinting. This Unit will encompass the activity already carried out at the Donostialdea IHO on bio-model printing, together with a new development in the area of bio-inks and 3D bioprinting. Development of the 3D printing area is currently one of the strategic R&D&I endeavours at the Biodonostia HRI.

The introduction of 3D technology to the biomedical field has two main areas of application. On the one hand, the creation of bio-models, understanding as such modelling of the disease (mainly tumours) in order to improve surgical approximation and patient operating times, as well as to personalise prosthetic implants. On the other hand, the bioprinting of cells and tissues for their use in approximations based on regenerative medicine.

The use of plastic models enabling an exact 3D replica of the characteristics of each patient’s tumour has a number of advantages, such as improved planning of surgery before proceeding, improving trust in the most suitable surgical approximation, shorter operating times and a possible improvement in the customised adaptation of prostheses and implants to each patient’s anatomy. In turn, the patient obtains an improved visualisation of their pathology and better understanding of the risks associated to the operation, thereby improving their trust in the medical team and reducing their anxiety in relation to the operation. In recent years the bio-models area has acquired considerable development in our environment thanks to interaction between the Thoracic Surgery Service of the Donostia University Hospital (DUH), now the Donostialdea Integrated Health Organisation (Donostialdea IHO), the X-ray Diagnostics Service, also belonging to the Donostialdea IHO, the San Sebastian School of Engineering, the Tknika Vocational Education Centre in Errenteria (Gipuzkoa), and other actors, having already gained position as one of the national benchmark units in this field. Translation to the clinic is now a reality, with 36 models having been designed and dispatched to 23 national hospitals, added to which are another 19 models designed for this particular Service and for other Hospital services.

On the other hand, the bio-ink and 3D bioprinting development area is less developed, having been limited until now to the pioneer initiative of the IHO Ear, Nose and Throat Service, leading to the acquisition and setting in motion of a 3D bioprinter at the Biodonostia HRI thanks two Bottom Up projects corresponding to the Operating Contract (granted by the Ministry of Health’s Provincial Delegation for Gipuzkoa). To strengthen this area, new equipment has been acquired, financed thanks to the Medtech initiative (promoted by the Presidency of the Basque Government and the Ministry of Health, through the Innovation Fund). Projects are also being set in motion with the focus on different pathologies in the areas of oncology, urology and surgery.

The intention on creating this new Unit is to promote the two 3D printing areas, formalising and intensifying the collaboration between biomedical professionals in different branches, engineers and vocational education technicians (VE). Furthermore, the creation of a Platform/Multidisciplinary Unit constitutes an opportunity to provide the service to other national healthcare centres and in so doing to multiply returns on the investment, also favouring competitiveness of the Institute researchers in regard to obtaining European funding.

Biodonostia, world leaders with a project on head and neck cancer

Charles Lawrie & Lorea Manterola /Photo Usoz

A report published in the Diario Vasco newspaper towards the end of the year refers to the current situation of a research project carried out at Biodonostia on head and neck cancer by Charles Lawrie, an Ikerbasque researcher and head of the Institute’s Oncology area, together with Lorea Manterola, a member of the centre’s Molecular Oncology Group.

The origin of the report is the publication in the prestigious Scientific Reports journal of a scientific study on the early detection of head and neck cancer, and specifically on DNA biomarkers for the early detection of laryngeal cancer carried out at Biodonostia by the Institute’s Molecular Oncology group. Said report mentions a number of questions, such as the value of achieving a good diagnosis of premalignant lesions in order to be able to study their mutations and learn whether or not they will develop into cancer, with the importance this entails for their treatment. It also mentions the interest shown by hospitals from all over Northern Spain with respect to collaborating in the project.

See the whole interview on:

Link of the Diario Vasco

PDF of the article