The generation of induced pluripotent stem cells (iPSCs), especially the generation of patient-derived pluripotent stem cells suitable for disease modelling in vitro, opens the door for the potential translation of stem-cell related studies into the clinic.
Successful replacement, or augmentation, of the function of damaged cells by patient derived differentiated stem cells would provide a novel cell-based therapy for diseases. Since iPSCs resemble human embryonic stem cells (hESCs) in their ability to generate cells of three germ layers, patient-specific iPSCs offer definitive solutions for the ethical and histo-incompatibility issues related to hESCs. Indeed human iPSC (hiPSC)-based autologous transplantation is heralded as the future of regenerative medicine.
Figure 1: Patient induced pluripotent stem cells (iPSCs) represent an unprecedented tool for the generation of in vitro platforms for disease modelling and the definition of protocols for pluripotent stem cells differentiation. Transdifferentiation also offers the possibility to generate auto-compatible cells with no need to undergo to pluripotent stage. In these scenarios the correction of the genetic defect(s) leading to disease may help to understand the molecular and cellular mechanisms driving disease gestation and progression, and more importantly, to identify novel mechanisms leading to organ regeneration. The combination of gene editing methodologies with defined protocols for tissue differentiation helps us to generate in vitro systems for drug screening and disease modelling.
One of our aims is to generate and correct disease-specific hiPSCs for disease modelling and drug screening. The combination of gene-editing based methodologies together with the development of novel protocols for cell differentiation into relevant tissues/organs, provides a unique scenario for modelling disease progression, and the identification of molecular and cellular mechanisms leading to organ regeneration (Figure 1). In this regard we are particularly interested in generation of transgene-free and disease free patient derived hiPSCs for disease modelling and the discovery of novel therapeutic targets.
We believe that the recovery of tissue function should not be restricted to the development of cell replacement therapies. In this regard, in our laboratory we take advantage of organisms that possess the ability to regenerate such as zebrafish, in order to understand which molecular and cellular pathways lead to organ regeneration. Surprisingly, studies in neonatal mice have demonstrated that soon after birth this organism posses the capability to regenerate its heart. Taking advantage of such preliminary observations we are translating such analysis in order to understand if the mammalian neonatal kidney still posses the capability to regenerate, and more importantly, if we are able to dissect the epigenetic and cellular mechanisms leading to those responses.
Lastly, and in an effort to fully develop in vitro and ex vivo platforms for organ regeneration, in our lab we are focused in the development of reporter cell lines for different transcription factors essential for tissue-specific commitment and differentiation (i.e: renal and cardiac lineages). The possibility to combine pluripotent stem cell lines together with decellularized matrices, functionalized biomaterials and ex vivo organoids offers and unprecedented opportunity for the immediate generation of patient-specific in vitro and ex vivo platforms for disease modelling and organ regeneration (Figure 2).
Figure 2: Induced pluripotent stem cells (iPSCs) resemble human embryonic stem cells (hESCs) in their ability to generate cells of the three germ layers of the embryo. This capacity can help us to understand the molecular and cellular cues driving cell fate. Our aim is to generate reporter cell lines from patient iPSCs in order to develop robust protocols for pluripotent stem cells differentiation. Moreover, the combination of patient differentiated populations together with functionalized biomaterials, ex vivo approaches (i.e: organoids), and decellularized tissue matrices, offers and unprecedented strategy for organ regeneration.
Núria Montserrat Pulido | Junior Group Leader
Elena Garreta Bahima | Senior Researcher
Federico González Grassi | Senior Researcher
Carmen Hurtado Del Pozo | Postdoctoral Researcher
Carolina Tarantino | Senior Technician
Andrés Marco Giménez | PhD Student
Patricia Katherine Prado Peralta | PhD Student
Idoia Lucía Selfa Aspiroz | PhD Student
Benedetta Coppe | Masters Student
Luis Galán Palma | Masters Student
Maria Gallo | Masters Student
Mireia Samitier Martí | Laboratory Assistant
Sergi Àngel Bonilla Pons | Visiting Researcher
Blanca Molins Monteys | Visiting Researcher
Federico González Grassi, a senior researcher in the Pluripotency for organ regeneration group, recently gave an interview to Scitech Europa, a website that provides news and developments from the European science and technology community.
Nuria Montserrat features in a long article in Quo magazine.
In an article in El Periodico on Friday, five Barcelona-based scientists – including IBEC’s Josep Samitier, Nuria Montserrat and Paul Verschure – took stock of the possibilities of disciplines such as bioengineering and robotics to regenerate, recycle or even create life.
An IBEC group’s project was granted funding from the Fundación Científica de la Asociación Española Contra el Cáncer in their 2017 Ayudas LAB AECC call.
Nuria Montserrat features in an article in El Periodico today which discusses the possibilities offered by 3D bioprinting to create replacement tissues or even whole organs.
Yesterday IBEC appeared on Canal 33’s “El día de demà” programme in an episode about disease.
Yesterday, La Sexta broadcast the documentary “El futuro en 3D” about the different options offered by 3D printing.
An article about Nuria Montserrat appeared in El Mundo on Tuesday following her invovlement in a recent study in which the first human heart grafts from human pluripotent stem cells were generated.
In El Periodico today, there’s a four-page article about Catalonia’s ‘champion scientists’.
Scientists from IBEC, in collaboration with the Hospital General Universitario Gregorio Marañón in Spain and two other groups in the USA, have made a big leap in heart regeneration advances by achieving heart grafts from human pluripotent stem cells for the first time in less than one month.
In the magazine Ara, IBEC group leader Nuria Montserrat and artist Marcel·lí Antúnez, who creates interactive sculpture with organic materials, such as Joan l’Home de Carn, appeared in an article together talking about organ regeneration.
Researchers at the Hospital Clínic, IDIBAPS, the Hospital Sant Joan de Deu and the Institute for Bioengineering of Catalonia (IBEC) have participated in a study, led by Dr. Juan Carlos Izpisúa Belmonte of the Gene Expression Laboratory at California’s Salk Institute, that uses molecular “scissors” to remove mitochondrial mutations in mouse eggs.
New IBEC group leader Nuria Montserrat is featured in an article in El Mundo.
|REGMAMKID How to regenerate the mammalian kidney (2015-2020)||European Commission, ERC-StG||Nuria Montserrat|
|Red TerCel Red de Terapia Celular (2017-2021)||ISCIII||(Collaborator)|
|CHONDREG Identification of the epigenetic mechanisms preventing chondrocyte de-differentiation: generation of novel therapeutic strategies for the treatment of cartilage chronic osteochondral lesions||CIBER||Nuria Montserrat|
|Infarto de miocardio en jóvenes. Factores epigeneticos y nuevos marcadores de riesgo cardiovascular. Efecto de la modulación de la expresión de microRNAs y long-non coding RNAs||ISCIII||(Collaborator)|
|REPROMICRO Reprogramacion y regeneracion tisular a partir de microvesiculas derivadas de celulas madre de pluripotencia inducida (2017-19)||Ministerio de Economía y Competitividad, Explora Ciencia||Nuria Montserrat|
|Generation of Isogenic Models of Clear Cell Renal Cell Carcinoma (ccRCC) using CRISPR-engineered Kidney Organoids, for the identification of diagnostic biomarkers (2017-2020)||Fundación AECC||Nuria Montserrat|
|Desarrollo de nuevas estrategias para el tratamiento de la enfermedad renal(2015-2017)||MINECO||Nuria Montserrat|
|TRATENFREN Desarrollo de nuevas estrategias para el tratamiento de la enfermedad renal (2015-2017)||MINECO, Retos investigación: Proyectos I+D||Nuria Montserrat|
|Regenerative medicine for Fanconi anemia: generation of disease-free patient-specific iPS (2013-2016)||Fundació La Marató de TV3||Nuria Montserrat|
Garreta, Elena, Montserrat, Nuria, Belmonte, Juan Carlos Izpisua, (2018). Kidney organoids for disease modeling Oncotarget 9, (16), 12552-12553
Garreta, E., González, F., Montserrat, N., (2018). Studying kidney disease using tissue and genome engineering in human pluripotent stem cells Nephron 138, 48-59
Garreta, Elena, Oria, Roger, Tarantino, Carolina, Pla-Roca, Mateu, Prado, Patricia, Fernández-Avilés, Francisco, Campistol, Josep Maria, Samitier, Josep, Montserrat, Nuria, (2017). Tissue engineering by decellularization and 3D bioprinting Materials Today 20, (4), 166-178
Climent, A. M., Hernandez-Romero, I., Guillem, M. S., Montserrat, N., Fernandez, M. E., Atienza, F., Fernandez-Aviles, F., (2017). High resolution microscopic optical mapping of anatomical and functional reentries in human cardiac cell cultures IEEE Conference Publications Computing in Cardiology Conference (CinC), 2016 , IEEE (Vancouver, Canada) 43, 233-236
Garreta, Elena, Marco, Andrés, Eguizábal, Cristina, Tarantino, Carolina, Samitier, Mireia, Badiola, Maider, Gutiérrez, Joaquín, Samitier, Josep, Montserrat, Nuria, (2017). Pluripotent stem cells and skeletal muscle differentiation: Challenges and immediate applications The Plasticity of Skeletal Muscle: From Molecular Mechanism to Clinical Applications (ed. Sakuma, Kunihiro), Springer Singapore (Singapore, Singapore) online, 1-35
Xia, Yun, Montserrat, Nuria, Campistol, Josep M., Izpisua Belmonte, Juan Carlos, Remuzzi, Giuseppe, Williams, David F., (2017). Lineage reprogramming toward kidney regeneration Kidney Transplantation, Bioengineering and Regeneration (ed. Orlando, G., Remuzzi, Giuseppe, Williams, David F.), Academic Press (London, UK) , 1167-1175
Garreta, Elena, Marco, Andres, Izpisua Belmonte, Juan Carlos, Montserrat, Nuria, (2016). Genome editing in human pluripotent stem cells: a systematic approach unrevealing pancreas development and disease Stem Cell Investigation 4, (11), 1-4
Garreta, E., de Oñate, L., Fernández-Santos, M. E., Oria, R., Tarantino, C., Climent, A. M., Marco, A., Samitier, M., Martínez, Elena, Valls-Margarit, M., Matesanz, R., Taylor, D. A., Fernández-Avilés, F., Izpisua Belmonte, J. C., Montserrat, N., (2016). Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts Biomaterials 98, 64-78
Eguizabal, C., Herrera, L., De Oñate, L., Montserrat, N., Hajkova, P., Izpisua Belmonte, J. C., (2016). Characterization of the epigenetic changes during human gonadal primordial germ cells reprogramming Stem Cells 34, (9), 2418-2428
Castaño, J., Herrero, A. B., Bursen, A., González, F., Marschalek, R., Gutiérrez, N. C., Menendez, P., (2016). Expression of MLL-AF4 or AF4-MLL fusions does not impact the efficiency of DNA damage repair Oncotarget 7, (21), 30440-30452
Montserrat, N., Garreta, E., Izpisua Belmonte, J. C., (2016). Regenerative strategies for kidney engineering FEBS Journal 283, (18), 3303-3324
González, F., (2016). CRISPR/Cas9 genome editing in human pluripotent stem cells: Harnessing human genetics in a dish Developmental Dynamics 245, (7), 788-806
Vélez, E. J., Lutfi, E., Azizi, S., Montserrat, N., Riera-Codina, M., Capilla, E., Navarro, I., Gutiérrez, J., (2016). Contribution of in vitro myocytes studies to understanding fish muscle physiology Comparative Biochemistry and Physiology, Part - B: Biochemistry and Molecular Biology 199, 67-73
Garreta, Elena, Sanchez, Sonia, Lajara, Jeronimo, Montserrat, Nuria, Belmonte, Juan Carlos Izpisua, (2015). Roadblocks in the path of iPSC to the vlinic Current Transplantation Reports 5, (1), 14-18
Reddy, Pradeep, Ocampo, Alejandro, Suzuki, Keiichiro, Luo, Jinping, Bacman, Sandra , Williams, Sion, Sugawara, Atsushi, Okamura, Daiji, Tsunekawa, Yuji, Wu, Jun, Lam, David, Xiong, Xiong, Montserrat, Nuria, Esteban, Concepcion, Liu, Guang-Hui, Sancho-Martinez, Ignacio, Manau, Dolors, Civico, Salva, Cardellach, Francesc, del Mar O'Callaghan, Maria, Campistol, Jaime, Zhao, Huimin, Campistol, Josep, Moraes, Carlos, Izpisua Belmonte, Juan Carlos, (2015). Selective elimination of mitochondrial mutations in the germline by genome editing Cell 161, (3), 459-469
de Oñate, L., Garreta, E., Tarantino, C., Martínez, Elena, Capilla, E., Navarro, I., Gutiérrez, J., Samitier, J., Campistol, J.M., Muñoz-Cánovas, P., Montserrat, N., (2015). Research on skeletal muscle diseases using pluripotent stem cells Muscle Cell and Tissue (ed. Sakuma, K.), InTech (Rijeka, Croatia) , 333-357
- Real Time QuantStudio 5
- SimpliAmp thermocycler
- Eppendorf 5415D centrifuge
- Allegra X-15 R centrifuge
- Gyrozen 1248 centrifuge
- BioUltra 6 Telstar culture Hood 2x
- AH-100 Telstar primary culture Hood
- Binder CB 60 incubators 2x
- Controltecnica ASTEC SCA 165 incubator
- Controltecnica ZC 180 incubator
- Bioruptor Pico sonicator
- Thermomixer C thermal block
- Leica DMS1000 and DMIL Led microscopes
- Leica DMi1 microscope
- Leica MZ 10F magnifying glass
- Safe Imager 2.0 transilluminator
- Juan Carlos Izpisua Belmonte
Salk Institute for Biological Studies
- Dr. Josep Maria Campistol Plana
Experimental Laboratory of Nephrology and Transplantation, Hospital Clínic, Barcelona
- Peter Hohestein
The Roslin Institute, University of Edinburgh
- Dr. Pere Gascón Vilaplana
Head of Oncology Service/Molecular and Translational Oncology Laboratory, IDIBAPS
- Gloria Calderon
- Pura Muñoz Cánovas
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
- Dr. Pedro Guillén
Director Clínica Cemtro, Madrid
- Dr. Francisco Fernández Avilés
Head of Cardiology Service, Hospital General Universitario Gregorio Marañón, Madrid
- Dr María Eugenia Fernández
Unit of Cell Production, Hospital Gregorio Marañón, Madrid
- Joaquin Gutiérrez Fruitós
University of Barcelona
- Dr. Pere Roca-Cusachs
- Dr. Elena Martínez
- Dr. Cristina Eguizabal Argaiz
Centro Vasco de Transfusion y Tejidos Humanos (CVTTH), Bizkaia
- Dr. Antonio Alcaraz
Head of Urology, Hospital Clínic, Barcelona
- Dr. Oriol Casanovas
Head of Tumour Angiogenesis Group, IDIBELL