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Bioengineering in reproductive health

Samuel Ojosnegros Martos
Head of Bioengineering in Reproductive Health

ABOUT

The first Open Innovation Lab research unit at IBEC will be Bioengineering in Reproductive Health @Biorephealth, led by Dr. Samuel Ojosnegros.

The main research focus of our lab is to study the development of human and mouse embryos. We combine bioengineering and optics tools to generate novel technologies that allow us to study the mechanisms controlling mammalian embryo implantation. Our proprietary solutions can be used to improve in vitro fertilization (IVF) and have been licensed by the pharma industry. The strong translational component of our research is not limited to embryology but convey into other disciplines such as diagnostics and cell therapies.

The development of the embryo E in humans (and mammals in general) requires the embryo to implantat, which proceeds with the attachment of the embryo into the walls of the mother uterus and invasion of the tissue to form the placenta. This process is crucial for natural conception and especially for in vitro fertilization (IVF) as only 30% of IVF embryos successfully implant into the mother uterus’ and develop to term. However, despite the importance of implantation in human fertility, this process is still elusive for experimentation because the uterus is rather inaccessible and difficult to be analysed

In our lab we create microscopes and bioengineered platforms to study the 3D environments that support embryonic development outside of the mother uterus.   Our systems allow us to interrogation of the genetics, metabolomics and mechanics of the embryo in a high throughput manner. Using our systems, we are capable to (i) improve embryo culture conditions and (ii) diagnose embryos with improved implantation potential.

Our dual research philosophy with a basic-translational component, has granted us collaboration contracts with the pharma industry, hospitals, and venture capital to bring our technology to the clinics and to the market. Our innovative Open Lab is a multidisciplinary environment where biologists, biophysicists, clinicians, and business developers synergize to create a unique environment shaped by science and entrepreneurship.

Molecular mechanisms of embryo implantation


Human reproduction is surprisingly inefficient compared to other mammalian species. On average, 25–30% of natural conceptions lead to successful live births. IVF leads to a successful live birth only in about 30% of the times (averaged per embryo transferred). Around 60% of all conceptions are lost at the time of (or soon after) implantation. Implantation is not only a cornerstone of reproduction but an evolutionary novelty of mammals.

During implantation, the embryo at blastocyst stage attaches to the epithelial lining of the uterus (the endometrium). A specialized embryonic tissue, termed the trophoblast, invades the endometrium reaching out and connecting to the blood vessels. The trophoblast will give rise to the placenta and umbilical cord allowing continuous nutrient supply to the embryo and consequently a prolonged intrauterine retention of the embryo during pregnancy. However, the study of implantation is mainly inaccessible because it takes place inside the adult. To overcome this problem, we have developed proprietary culture methods and ex vivo implantation platforms which mimic the uterine microenvironment, allowing the embryo to progress towards post-implantation stages in an amenable way for optical microscopy.

Development of Human Plasma-Derived Protein Supplement to Improve Embryo Culture and Promote Embryo Implantation

Embryo culture in vitro from one cell stage to blastocyst stage in IVF clinics is carried out using human serum albumin (HSA). However non-clinical grade serums (such as FBS) have the potential to push the development of embryos further, but of course they cannot be used in the clinics. In the last years, in collaboration with GRIFOLS we have co-developed serums with batch consistency and clinical approval to culture human embryos. In addition to albumin these serums also provide growth factors, vitamins and other components that are removed during the purification process of albumin. This cocktail improves the efficiency of the development towards blastocyst stage and promote embryo ex vivo implantation.

Spectroscopy and label-free imaging

Spectroscopy refers to a family of imaging techniques which aim to extract information from the sample signal beyond the intensity profile. These techniques provide an additional dimension (i.e., spectral, oligomeric) to the image acquired.

Label-free microscopy, such as the imaging of autofluorescence signals from the cells, provide metabolic information of living tissues when analyzed using multispectral techniques.

In our lab we have specialized in spectroscopy imaging with emphasis on label-free methods. These methods are non-invasive, they do not require staining or sample manipulation whatsoever. For these reasons label-free imaging enables us to bring state-of-the-art microscopy techniques from the lab into the clinics, and study samples of biomedical relevance undisturbed at unprecedented level of detail.

Enhanced Number and Brightness a novel Imaging technique reveals protein dynamics in live cells

Proteins continuously interact with other proteins in the cell yet revealing these interactions in live-cell microscopy is technically challenging. Using statistical tools, we designed the Enhanced Number and Brightness method, which quantifies and maps protein aggregation in live cells in high resolution movies.
Several fluorescence microscopy methods are used to measure protein interactions in cells.  However, most of these methods struggle to capture both the diversity of these interactions across the entire cellular area and their dynamics over time.  To overcome these limitations, we enhanced the spatiotemporal resolution of Number and Brightness, a spectroscopy method that transforms fluorescence fluctuations into protein aggregation values.

The Enhanced Number and Brightness method implements two algorithms, the first one uses statistical tools to extract the distribution of protein oligomers (monomers, dimers, trimers and so on) in single pixels, thus revealing protein diversity across an entire cell image.  The second one corrects the fluorescence intensity loss due to continuous light exposure, which enables measurements over prolonged periods of time. By combining these two algorithms, Enhanced Number and Brightness allows extended live imaging, providing dynamic maps of protein oligomerization overlaid on top of the corresponding cell image.

Figure: Enhanced Number and Brightness provides oligomerization maps (color-coded according to reference bar) during time-lapse movies. The image shows from left to right the dynamics of Eph receptor aggregation after stimulation with the ligand Ephrin. Each row depicts a cell stimulated with different types of ligands (i.e. soluble, surface-bound etc.).

STAFF

PROJECTS

European Projects
HSMe-ImPredict · Development of non-invasive imaging methodology for improving embryo implantation prediction, via hyper-spectral metabolic profiling (2022-2024)Marie Curie Individual FellowshipSamuel Ojosnegros
National projects
HYSPLANT · Selección de embriones para fecundación in vitro: predicción del éxito de implantación mediante clasificación metabólica de embriones (2020-2023)MINECO
Retos investigación: Proyectos I+D
Samuel Ojosnegros
Prediction of implantation success by hyperspectral metabolic profiling of human embryos obtained by in vitro fertilization (2020-2022)AGAUR
Beatriu de Pinós 2018
Samuel Ojosnegros
Private sector
Estudio del mecanismo de acción de OXO-001 (2020-2022)OxolifeSamuel Ojosnegros
Evaluación de derivados plasmáticos humanos para el cultivo de embriones (2019-2021)IVFTECH S.L.Samuel Ojosnegros
Evaluación de derivados plasmáticos humanos para el cultivo de células mesenquimales y CAR-T (2020-2022)IVFTECH S.L.Samuel Ojosnegros
Prediction of implantation success by single-cell transcriptomic profiling of human embryos obtained by in vitro fertilization (2018-2022)Scranton Enterprises BVSamuel Ojosnegros
Finished projects
HYSPLANT · Metabolic profiling of in vitro fertilization embryos using hyspectral imaging (2019-2020)European Commission ATTRACTSamuel Ojosnegros
Embryo on a chip: Smart microdevice development for high-throughput screening embryo implantation (2020)Tecniospring 2020Maria Demestre Viladevall

NEWS

 

El grupo Bioingeniería en salud reproductiva del Instituto de Bioingeniería de Cataluña (IBEC) aparece a los medios por su participación en el desarrollo de un dispositivo que ofrezca información metabólica del óvulo antes de criopreservar-lo. … Read more

Desarrollan una técnica pionera para saber si un óvulo es bueno

El grupo Bioingeniería en salud reproductiva del Instituto de Bioingeniería de Cataluña (IBEC) aparece a los medios por su participación en el desarrollo de un dispositivo que ofrezca información metabólica del óvulo antes de criopreservar-lo. … Read more

El proyecto HYLIGHT, coordinado por Samuel Ojosnegros del IBEC, ha sido seleccionado para la fase 2 de la convocatoria ATTRACT, una iniciativa de la Unión Europea para impulsar la transferencia de tecnologías con gran potencial de los laboratorios a la sociedad. El proyecto será financiado con cerca de 2 millones de euros durante 26 meses y tiene como objetivo desarrollar un dispositivo de diagnóstico para seleccionar embriones basándose en sus perfiles metabólicos y aumentar las tasas de éxito de las técnicas de fertilización in vitro.

Investigadores del IBEC forman parte del proyecto europeo ATTRACT para desarrollar un dispositivo de diagnóstico que mejore la selección de embriones para los procedimientos de fertilización in vitro

El proyecto HYLIGHT, coordinado por Samuel Ojosnegros del IBEC, ha sido seleccionado para la fase 2 de la convocatoria ATTRACT, una iniciativa de la Unión Europea para impulsar la transferencia de tecnologías con gran potencial de los laboratorios a la sociedad. El proyecto será financiado con cerca de 2 millones de euros durante 26 meses y tiene como objetivo desarrollar un dispositivo de diagnóstico para seleccionar embriones basándose en sus perfiles metabólicos y aumentar las tasas de éxito de las técnicas de fertilización in vitro.

El projecto REACT, liderado por el Statens Serum Institut de Dinamarca, cuenta con la participación del Instituto de Bioingeniería de Cataluña (IBEC) que, con un presupuesto cercano al millón de euros de un total de siete, generará organoides epiteliales nasales humanos específicos como plataformas de validación y modelos preclínicos para investigar la interacción huésped-patógeno .

El IBEC recibe cerca de un millón de euros para estudiar las enfermedades respiratorias graves causadas por virus

El projecto REACT, liderado por el Statens Serum Institut de Dinamarca, cuenta con la participación del Instituto de Bioingeniería de Cataluña (IBEC) que, con un presupuesto cercano al millón de euros de un total de siete, generará organoides epiteliales nasales humanos específicos como plataformas de validación y modelos preclínicos para investigar la interacción huésped-patógeno .

Más de trescientos expertos internacionales en el campo de la investigación en terapias regenerativas se citaron en el simposio organizado por el Instituto de Bioingeniería de Catalunya (IBEC) para presentar los últimos avances en miniórganos, órganos en un chip, bioimpresión 3D e ingeniería de tejidos, entre otros.

Las terapias regenerativas del futuro confluyeron en el Simposio IBEC, con expertos internacionales y más de 300 inscritos

Más de trescientos expertos internacionales en el campo de la investigación en terapias regenerativas se citaron en el simposio organizado por el Instituto de Bioingeniería de Catalunya (IBEC) para presentar los últimos avances en miniórganos, órganos en un chip, bioimpresión 3D e ingeniería de tejidos, entre otros.

Oxolife, la startup biotecnológica focalizada en el desarrollo de fármacos para la mejora de la fertilidad femenina, y el Laboratorio de Bioingeniería en Salud Reproductiva del Instituto de Bioingeniería de Cataluña (IBEC), combinarán dos tecnologías pioneras para el estudio y tratamiento de la infertilidad.

IBEC y Oxolife inician un estudio pionero para tratar la infertilidad

Oxolife, la startup biotecnológica focalizada en el desarrollo de fármacos para la mejora de la fertilidad femenina, y el Laboratorio de Bioingeniería en Salud Reproductiva del Instituto de Bioingeniería de Cataluña (IBEC), combinarán dos tecnologías pioneras para el estudio y tratamiento de la infertilidad.

Application Deadline: 15/07/2020Ref: SR-SO The Bioengineering in reproductive health group at the Institute for Bioengineering of Catalonia (IBEC) is looking for a Senior Scientist to develop a project in collaboration with the industry. The project involves investigate the molecular mechanisms affected by specific chemical treatments on endometrial receptivity and on mouse and human embryos in culture. We aim to combine the expertise in microscopy of the lab with embryology tools to understand the morphological and molecular modifications that lead to an increase in endometrial receptivity. An ideal candidate will have experience in the mouse or human embryology field and will know basic tools of molecular biology. The candidate will have a great degree of independence to coordinate the project, competitive salary and funding to outsource several tests (i.e. sequencing, histology etc.). Our laboratory is a multidisciplinary environment where biologists, biophysicists, clinicians and business developers synergize to create a unique environment shaped by science and entrepreneurship. Due to the high translational component of our research, we have established collaboration contracts with the pharma industry, hospitals and venture capital to bring our technology to the clinics and the market. In our lab we use bioengineering methods to create 3D environments that support embryonic development outside of the mother uterus. Our systems are accessible to imaging tools which allow us to interrogate the genetics, metabolomics and mechanics of the embryo in a high throughput manner. Using our systems we are capable to (i) improve embryo culture conditions and (ii) diagnose embryos with improved implantation potential.

Senior researcher at the Bioengineering in Reproductive Health Research Group

Application Deadline: 15/07/2020Ref: SR-SO The Bioengineering in reproductive health group at the Institute for Bioengineering of Catalonia (IBEC) is looking for a Senior Scientist to develop a project in collaboration with the industry. The project involves investigate the molecular mechanisms affected by specific chemical treatments on endometrial receptivity and on mouse and human embryos in culture. We aim to combine the expertise in microscopy of the lab with embryology tools to understand the morphological and molecular modifications that lead to an increase in endometrial receptivity. An ideal candidate will have experience in the mouse or human embryology field and will know basic tools of molecular biology. The candidate will have a great degree of independence to coordinate the project, competitive salary and funding to outsource several tests (i.e. sequencing, histology etc.). Our laboratory is a multidisciplinary environment where biologists, biophysicists, clinicians and business developers synergize to create a unique environment shaped by science and entrepreneurship. Due to the high translational component of our research, we have established collaboration contracts with the pharma industry, hospitals and venture capital to bring our technology to the clinics and the market. In our lab we use bioengineering methods to create 3D environments that support embryonic development outside of the mother uterus. Our systems are accessible to imaging tools which allow us to interrogate the genetics, metabolomics and mechanics of the embryo in a high throughput manner. Using our systems we are capable to (i) improve embryo culture conditions and (ii) diagnose embryos with improved implantation potential.

Application Deadline: 30/06/2020Ref: LT-SO The Bioengineering in Reproductive Health Group offers a lab technician position for an experienced cell culture technician to develop a project in collaboration with the industry. The project involves testing the effects of different cell culture supplements on several cell types (e.g. Mesenchymal Stromal Cells, CAR T Cells, etc.) Our laboratory is a multidisciplinary environment where biologists, biophysicists, clinicians and business developers synergize to create a unique environment shaped by science and entrepreneurship. Due to the high translational component of our research, we have established collaboration contracts with the pharma industry, hospitals and venture capital to bring our technology to the clinics and the market. In our lab, we develop high-tech projects in the fields of embryology, cell biology and imaging. Our strategy involves the development of new products for the pharmaceutical industry. The current position seeks a motivated cell culture technician with experience in diverse cell culture systems.

Cell culture lab technician at the Bioengineering in Reproductive Health Research Group

Application Deadline: 30/06/2020Ref: LT-SO The Bioengineering in Reproductive Health Group offers a lab technician position for an experienced cell culture technician to develop a project in collaboration with the industry. The project involves testing the effects of different cell culture supplements on several cell types (e.g. Mesenchymal Stromal Cells, CAR T Cells, etc.) Our laboratory is a multidisciplinary environment where biologists, biophysicists, clinicians and business developers synergize to create a unique environment shaped by science and entrepreneurship. Due to the high translational component of our research, we have established collaboration contracts with the pharma industry, hospitals and venture capital to bring our technology to the clinics and the market. In our lab, we develop high-tech projects in the fields of embryology, cell biology and imaging. Our strategy involves the development of new products for the pharmaceutical industry. The current position seeks a motivated cell culture technician with experience in diverse cell culture systems.

Santiago Marco, investigador principal del grupo de Procesamiento de señales e información para sistemas de sensores y Samuel Ojosnegros, responsable de la unidad Bioingeniería en Salud Reproductiva, han sido seleccionados por sus proyectos de investigación en la convocatoria del programa ATTRACT. La convocatoria recibió más de 1200 propuestas de las cuales se seleccionaron 170. El programa ATTRACT es un proyecto pionero de investigación e innovación que forma parte del programa Horizon 2020 financiado por la Unión Europea y respaldado por un consorcio formado por 9 socios. El objetivo principal de este programa es crear un ecosistema de innovación conjunta entre la investigación fundamental y las comunidades industriales para desarrollar tecnologías avanzadas de detección e imagen para usos científicos y comerciales.

Dos proyectos del programa ATTRACT para investigadores del IBEC

Santiago Marco, investigador principal del grupo de Procesamiento de señales e información para sistemas de sensores y Samuel Ojosnegros, responsable de la unidad Bioingeniería en Salud Reproductiva, han sido seleccionados por sus proyectos de investigación en la convocatoria del programa ATTRACT. La convocatoria recibió más de 1200 propuestas de las cuales se seleccionaron 170. El programa ATTRACT es un proyecto pionero de investigación e innovación que forma parte del programa Horizon 2020 financiado por la Unión Europea y respaldado por un consorcio formado por 9 socios. El objetivo principal de este programa es crear un ecosistema de innovación conjunta entre la investigación fundamental y las comunidades industriales para desarrollar tecnologías avanzadas de detección e imagen para usos científicos y comerciales.

El Instituto de Bioingeniería de Catalunya (IBEC) firma un acuerdo por una ronda de inversión inicial de un millón y medio de euros con Scranton Entreprises B.V. -una asociación de inversión con sede en los Países Bajos-, con el fin de desarrollar tecnología que prediga la probabilidad de implantación de embriones obtenidos mediante fecundación in vitro. Este acuerdo es el primero que se establece en el marco de la nueva iniciativa del instituto, el Open Innovation Lab, que ofrece a empresas e inversores una plataforma para llevar más ágilmente la investigación de vanguardia a los pacientes y al mercado.

El IBEC firma un acuerdo por 1.5 millones de euros con Scranton Enterprises

El Instituto de Bioingeniería de Catalunya (IBEC) firma un acuerdo por una ronda de inversión inicial de un millón y medio de euros con Scranton Entreprises B.V. -una asociación de inversión con sede en los Países Bajos-, con el fin de desarrollar tecnología que prediga la probabilidad de implantación de embriones obtenidos mediante fecundación in vitro. Este acuerdo es el primero que se establece en el marco de la nueva iniciativa del instituto, el Open Innovation Lab, que ofrece a empresas e inversores una plataforma para llevar más ágilmente la investigación de vanguardia a los pacientes y al mercado.

JOBS

PUBLICATIONS

S Ojosnegros, A Seriola, AL Godeau, A Veiga (2021) Embryo implantation in the laboratory: an update on current techniques. Human Reproduction Update, Vol.00, No.0, pp. 1–30.

Martin Plöschner, Denitza Denkova, Simone De Camillis, Minakshi Das, Lindsay M. Parker, Xianlin Zheng, Yiqing Lu, Samuel Ojosnegros, and James A. Piper (2020) Simultaneous super-linear excitation-emission and emission depletion allows imaging of upconversion nanoparticles with higher sub-diffraction resolution. Optics Express 28 (16), 24308-24326.

EQUIPMENT

  • Micromanipulation-microinjection station
  • Embryo biopsy laser
  • Embryo culture laboratory
  • Genome editing
  • In vitro fertilization
  • ICSI
  • Cell culture laboratory
  • 3D cell culture
  • Advanced live imaging: photoconversion, 3D imaging, light scattering, spectroscopy
  • Image analysis workstation

COLLABORATIONS

  • Prof. Anna Veiga – Barcelona Stem Cell Bank (IDIBELL) and Dexeus Mujer, Barcelona
  • Dr. Montserrat Boada/ Dr. Pere Barri – Dexeus Mujer, Barcelona
  • Dr. Ayelet Lesman – Tel Aviv University (TAU), Israel
  • Dr. Elena Martínez – IBEC
  • Dr. Francesco Cutrale, University of Southern California (USC), USA
  • Dr. Manuel Irimia – CRG, Barcelona
  • Dr. Javier Ramón – IBEC

ENTREPRENEURSHIP

· Jorge Fuentes,
   Business Strategy, A_Ventures, Barcelona, Spain

  

 

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