Staff member

Núria Montserrat Pulido

Junior Group Leader
Pluripotent Stem Cells and Activation of Endogenous Tissue Programs for Organ Regeneration
+34 934 031 391
CV Summary

Dr. Nuria Montserrat became interested in organ regeneration and stem cells during her master and PhD training that finished in 2006. The same year she got a Postdoctoral fellowship from the Fundaçao para a Ciência e Tecnología (Portugal). In 2007 she was hired as a post-doctoral researcher at the Hospital of Santa Creu i Sant Pau in Barcelona.
In 2008 she moved to the Center of Regenerative Medicine of Barcelona (CMRB) as a research associate. There, Dr. Montserrat participated in developing strategies for the generation and banking of new induced pluripotent stem cells (iPSCs).
In 2010 she first co-authored how to reprogram cord blood stem cells for the first time (Nature Protocols, 2010). Then she reasoned that iPSCs could be obtained by means of safe strategies with new factors. The work resulted in a high-impact publication in Cell Stem Cell (2013), in where she was the first co-author. She also collaborated in other projects aimed to characterize the genomic integrity of human iPSCs (Nature 2012) as well as in the differentiation of iPSCs towards different lineages (Stem Cells 2011; Nature 2012; Nature Methods 2012, Nature Cell Biology 2013, Nature Communications 2014). Dr. Montserrat has also participated in the generation of platforms for the study of disease progression by means of iPSCs (Nature 2012, Nature Communications 2014).
More recently, she has first co-authored how the reactivation of endogenous pathways can be artificially reactivated and promote heart regeneration in mammals (Cell Stem Cell, 2014). Her expertise in the fields of somatic reprogramming and organ regeneration helped her to develop a massive project was been selected for funding from the European Research Council within the ERC Starting Grant call of 2014.

Staff member publications

Garreta, E., de Oñate, L., Fernández-Santos, M. E., Oria, R., Tarantino, C., Climent, A. M., Marco, A., Samitier, M., Martínez, E., 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

Genome editing on human pluripotent stem cells (hPSCs) together with the development of protocols for organ decellularization opens the door to the generation of autologous bioartificial hearts. Here we sought to generate for the first time a fluorescent reporter human embryonic stem cell (hESC) line by means of Transcription activator-like effector nucleases (TALENs) to efficiently produce cardiomyocyte-like cells (CLCs) from hPSCs and repopulate decellularized human heart ventricles for heart engineering. In our hands, targeting myosin heavy chain locus (MYH6) with mCherry fluorescent reporter by TALEN technology in hESCs did not alter major pluripotent-related features, and allowed for the definition of a robust protocol for CLCs production also from human induced pluripotent stem cells (hiPSCs) in 14 days. hPSCs-derived CLCs (hPSCs-CLCs) were next used to recellularize acellular cardiac scaffolds. Electrophysiological responses encountered when hPSCs-CLCs were cultured on ventricular decellularized extracellular matrix (vdECM) correlated with significant increases in the levels of expression of different ion channels determinant for calcium homeostasis and heart contractile function. Overall, the approach described here allows for the rapid generation of human cardiac grafts from hPSCs, in a total of 24 days, providing a suitable platform for cardiac engineering and disease modeling in the human setting.

Keywords: Cardiac function, Extracellular matrix, Gene targeting, Pluripotent stem cells

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

Abstract: Epigenetic reprogramming is a central process during mammalian germline development. Genome-wide DNA demethylation in primordial germ cells (PGCs) is a prerequisite for the erasure of epigenetic memory, preventing the transmission of epimutations to the next generation. Apart from DNA demethylation, germline reprogramming has been shown to entail reprogramming of histone marks and chromatin remodelling. Contrary to other animal models, there is limited information about the epigenetic dynamics during early germ cell development in humans. Here, we provide further characterization of the epigenetic configuration of the early human gonadal PGCs. We show that early gonadal human PGCs are DNA hypomethylated and their chromatin is characterized by low H3K9me2 and high H3K27me3 marks. Similarly to previous observations in mice, human gonadal PGCs undergo dynamic chromatin changes concomitant with the erasure of genomic imprints. Interestingly, and contrary to mouse early germ cells, expression of BLIMP1/PRDM1 persists in through all gestational stages in human gonadal PGCs and is associated with nuclear lysine-specific demethylase-1. Our work provides important additional information regarding the chromatin changes associated with human PGCs development between 6 and 13 weeks of gestation in male and female gonads.

Keywords: Epigenetic, Human primordial germ cells, Reprograming

Montserrat, N., Garreta, E., Izpisua Belmonte, J. C., (2016). Regenerative strategies for kidney engineering FEBS Journal 283, (18), 3303-3324

The kidney is the most important organ for water homeostasis and waste excretion. It performs several important physiological functions for homeostasis: it filters the metabolic waste out of circulation, regulates body fluid balances, and acts as an immune regulator and modulator of cardiovascular physiology. The development of in vitro renal disease models with pluripotent stem cells (both human embryonic stem cells and induced pluripotent stem cells) and the generation of robust protocols for in vitro derivation of renal-specific-like cells from patient induced pluripotent stem cells have just emerged. Here we review major findings in the field of kidney regeneration with a major focus on the development of stepwise protocols for kidney cell production from human pluripotent stem cells and the latest advances in kidney bioengineering (i.e. decellularized kidney scaffolds and bioprinting). The possibility of generating renal-like three-dimensional structures to be recellularized with renal-derived induced pluripotent stem cells may offer new avenues to develop functional kidney grafts on-demand.

Keywords: Induced pluripotent stem cells, Kidney disease, Kidney engineering, Pluripotent stem cells, Renal differentiation

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

Research on the regulation of fish muscle physiology and growth was addressed originally by classical in vivo approaches; however, systemic interactions resulted in many questions that could be better considered through in vitro myocyte studies. The first paper published by our group in this field was with Tom Moon on brown trout cardiomyocytes, where the insulin and IGF-I receptors were characterized and the down-regulatory effects of an excess of peptides demonstrated. We followed the research on cultured skeletal muscle cells through the collaboration with INRA focused on the characterization of IGF-I receptors and its signaling pathways through in vitro development. Later on, we showed the important metabolic role of IGFs, although these studies were only the first stage of a prolific area of work that has offered a useful tool to advance in our knowledge of the endocrine and nutritional regulation of fish growth and metabolism. Obviously, the findings obtained in vitro serve the purpose to propose the scenario that will need confirmation in vivo, but this technique has made possible many different, easy, fast and better controlled studies. In this review, we have summarized the main advances that the use of cultured muscle cells has permitted, focusing mainly in the role of IGFs regulating fish metabolism and growth. Although many articles have already appeared using this model system in salmonids, gilthead sea bream or zebrafish, it is reasonable to expect new studies with cultured cells using innovative approaches that will help to understand fish physiology and its regulation.

Keywords: Amino acids, IGFs, In vitro cultures, Insulin, Insulin and IGF-I receptors, Myogenesis, Myogenic factors, TOR

de Oñate, L., Garreta, E., Tarantino, C., Martínez, E., 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

The generation of induced pluripotent stem cells (iPSCs), especially the generation of patient-derived pluripotent stem cells (PSCs) 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 skeletal muscle-related diseases. Since iPSCs resemble human embryonic stem cells (hESCs) in their ability to generate cells of the 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. Interestingly, during the last years intense research has been published on disease-specific hiPSCs derivation and differentiation into relevant tissues/organs providing a unique scenario for modelling disease progression, to screen patient-specific drugs and enabling immunosupression-free cell replacement therapies. Here, we revise the most relevant findings in skeletal muscle differentiation using mouse and human PSCs. Finally and in an effort to bring iPSC technology to the daily routine of the laboratory, we provide two different protocols for the generation of patient-derived iPSCs.

Keywords: Pluripotent stem cells, Myogenic differentiation, Disease modelling, Patient-specific induced pluripotent stem cells, Muscular dystrophy

Garcia, A., Hortigüela, V., Lagunas, A., Cortina, C., Montserrat, N., Samitier, J., Martinez, E., (2014). Protein patterning on hydrogels by direct microcontact printing: application to cardiac differentiation RSC Advances 4, (55), 29120-29123

An extended microcontact printing technique to chemically pattern hydrogels is reported. The procedure employs standard polydimethylsiloxane stamps and requires minor pre-processing of the hydrogels by freeze-drying. Micropatterned Matrigel[trade mark sign] and gelatin hydrogels induce NIH-3T3 cell alignment and elongation. Furthermore, human embryonic stem cells cultured on fibronectin-patterned hydrogels display beating foci earlier than those cultured on non-patterned substrates.

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