iBB

On the 16th of February 2023, Joaquim Cabral, former presidente of iBB,  gives a lecture at Sessão da Classe de Ciências of Academia das Ciências de Lisboa. This lecture will be entitled “The Role of Bioprocess Engineering and Cellular Therapies and Regenerative Medicine”. This session will be chaired by Professor Carlos Salema and will also feature a lecture given by Professor Conceição Peleteiro and several guests.

CellAgri Portugal, the Portuguese Association for Cellular Agriculture Development, is a recently created independent non-profit organization, headquartered at IST-TagusPark.

The mission of CellAgri Portugal is to facilitate and encourage the cooperative development of cellular_agriculture in Portugal as well as to inform the public about the industrial, scientific, and technological developments in the field involving the Portuguese community worldwide.

Joaquim Cabral is the president of CellAgri Portugal and Carlos Rodrigues is the executive director. CellAgri Portugal also counts with the iBB researchers Frederico Ferreira, Ana Fernandes-Platzgummer, Paola Alberte, and the iBB PhD students Diana Marques and Hélder Tavares.

A team of researchers from iBB-BERG, including Carlos Rodrigues, Ricardo Pereira, Pedro Fernandes, Prof. Joaquim Sampaio Cabral and led by Carla de Carvalho, will contribute to the development of enzymes for a new generation of environmentally friendly consumer products in the EU project FuturEnzyme. The consortium of 16 leading academic and industrial partners, led by Dr. Manuel Ferrer from CSIC (Spain), will develop innovative solutions that will combine big biodata mining and bio-prospecting, disruptive machine learning and protein engineering, nano-biotechnology, fermentation and downstream-processing systems, and pre-industrial testing. Innovative solutions will be proposed to discover, design, optimize and formulate new enzymes to develop detergents, textiles and cosmetics that combine a high level of functionality with improved sustainability, thus responding to the demands from consumers and industries.

Engineering brain organoids from human induced pluripotent stem cells (hiPSCs) is a powerful tool for modeling brain development and neurological disorders. Rett syndrome (RTT), a rare neurodevelopmental disorder, can greatly benefit from this technology, since it affects multiple neuronal subtypes in forebrain sub-regions. SCERG-iBB researchers have recently established dorsal and ventral forebrain organoids from control and RTT patient-specific hiPSCs recapitulating the 3D organization and functional network complexity of this brain region. The data obtained revealed a premature development of the deep-cortical layer, associated to the formation of TBR1 and CTIP2 neurons, and a lower expression of neural progenitor/proliferative cells in RTT dorsal organoids. Moreover, calcium imaging and electrophysiology analysis demonstrated functional defects of RTT neurons. Additionally, assembly of RTT dorsal and ventral organoids revealed impairments of interneuron’s migration. Overall, these models provide a better understanding of RTT during early stages of neural development, demonstrating a great potential for personalized diagnosis and drug screening. The paper was published in Frontiers in Cell Development Biology.

Umbilical cord blood (UCB) is an accepted and appealing alternative source of hematopoietic stem/progenitor cells (HSPC) for hematopoietic cell transplants. However, low UCB volume recovered from births results in an unsatisfactory cell dose for transplants in adults, having initially limited transplants of a single UCB unit to pediatric patients. Ex vivo expansion of HSPC based on the addition of exogenous cytokines.has been pursued to address this problem. Notably, selection of individual cytokines and their concentrations for an expansion cocktail has differed between existing strategies. To improve the effectiveness of these platforms, namely targeting clinical approval, iBB researchers optimized the cytokine cocktails in two clinically relevant expansion platforms for HSPC, a liquid suspension culture system (CS_HSPC) and a co-culture system with bone marrow derived mesenchymal stromal cells (CS_HSPC/MSC).. The tailored and novel optimized cocktails determined made it possible to individually maximize cytokine contribution in both studied platforms, leading to an increase in the expansion platform performance, while allowing a rational side-by-side comparison between them and enhancing our knowledge on the impact of cytokine supplementation on the HSPC expansion process. The results achieved were published in Frontiers in Bioengineering and Biotechnology, Stem Cell Systems Bioengineering section.

Bioreactors that provide different biophysical stimuli have been used in tissue engineering approaches aimed at enhancing the quality of the cartilage tissue generated. However, such systems are often highly complex, costly and not very versatile. In a recent study published in Biotechnology Journal, researchers from SCERG-iBB working with colleagues from the Polytechnic Institute of Leiria and Rensselaer Polytechnic Institute (USA) developed a novel, cost-effective and customizable perfusion bioreactor fabricated by additive manufacturing (AM) to study of the effect of fluid flow on the chondrogenic differentiation of human bone-marrow mesenchymal stem/stromal cells (hBMSCs) in 3D porous poly (ε-caprolactone) (PCL) scaffolds. Results suggest that the chondrogenic differentiation of hBMSCs was enhanced in cell-scaffold constructs cultured under perfusion and highlights the potential of customizable AM platforms for developing more reliable in vitro models and improved personalized cartilage repair strategies.

A video overview of the output of INMARE (‘Industrial Applications of Marine Enzymes’), a four-year European research project that set out to transform the enzyme biodiscovery process and to isolate new enzymes from the ocean, has been made available by the consortium. The goal of INMARE was to shorten & streamline the industrial enzyme pipeline by increasing the value of enzyme collections and to identify new lead products and prototypes during the projects lifetime. INMARE brought together several industrial and academic partners, including iBB-IST. The project received funding from the EU’s Horizon 2020 research and innovation programme under grant agreement No. 634486.

Photo details; sea shore by Cascais, Copyright Carla de Carvalho, 2017. 

Cell-derived ECM have emerged as promising materials for regenerative medicine due to their ability to recapitulate the native tissue microenvironment. However, little is known about the glycosaminoglycan (GAG) composition of these cell-derived ECM. In a recent study published in Glycoconjugate Journal, researchers from SCERG-iBB, working in collaboration with colleagues from the Rensselaer Polytechnic Institute, characterized three different cell-derived ECM in terms of their GAG content, composition and sulfation patterns using a highly sensitive LC-MS/MS technique. Distinct GAG compositions and disaccharide sulfation patterns were verified for the different cell-derived ECM. Additionally, the effect of decellularization method on the GAG and disaccharide relative composition was also assessed. The method offers a novel approach to determine the GAG composition of cell-derived ECM, which we believe is critical for a better understanding of ECM role in directing cellular responses and has the potential for generating important knowledge for the development of new ECM-like biomaterials for tissue engineering applications.

The December 16, 2022 Episode of 110 Stories | 110 Técnico objects is dedicated to Técnico’s first registered patent. That 1985´s  patent, entitled "PROCESS FOR THE PRODUCTION OF NATURAL SPARKLING WINES BY MEANS OF IMMOBILIZED YEAST" also belongs to the history of iBB. Indeed, iBB is the current research unit of the excellent lineage originating from the Laboratory of Biochemical Engineering/CEBQ-Center of Biological and Chemical Engineering. The first author was Júlio Maggiolly Novais, the founding director of that IST research unit. The other IST authors were Isabel Sá-Correia, Joaquim S Cabral and Manuela Cadete. In addition to IST, there were two other applicants: Instituto Superior de Agronomia (co-author: Prof Virgílio Loureiro) and Caves Raposeira LDA.
In this episode of the podcast, two of the authors intervened and explained the objectives and innovation related to the patent. The innovation consisted of immobilizing (sequestering in in an agar-agar gel) the yeast cells that carry out the secondary alcoholic fermentation in the bottle, typical of champagne production (to create the typical "bubbles" of CO2 gas). The objective was to make unnecessary the manual rotation of sparkling wine bottles, for three weeks, to remove the yeasts which, when free, accumulate in high concentrations making the drink very cloudy. During the podcast, it was also recalled the bottling carried out at Caves da Raposeira, applying the methods developed at the Técnico's laboratory to the reality of sparkling wine production. 

Six researchers from @IBB have been ranked among the World’s Top 2% of most widely cited scientists in the 2022 List of outstanding researchers prepared by Elsevier BV, and Stanford University (USA).   

Carla Carvalho, Joaquim Cabral, Isabel Sá Correia,  Mário Berberan e Santos, Miguel Prazeres and Pedro Fonte were recognized for the impact throughout their careers, while Pedro Fernandes was recognized as one of the World’s Top 2%  influent scientist in his field.

The updated list is based on the Sep 01-2022 SCOPUS database, updated to the end of the citation year 2021 and analyses 22 scientific areas and 176 disciplines.

Overall, 93 researchers from Técnico were highlighted in the study.  Congratulations to all!

Endogenous human brain tissue is not easily available for studying neurodevelopment and neurodegenerative diseases. However, human pluripotent stem cells (PSCs) have been used to generate a variety of glial and neuronal cells of the central nervous system. Still, reproducible protocols for generating in vitro models of the human cerebellum are scarce. In this context, Silva et al. describe the scalable production of human PSC-derived cerebellar organoids using single-use vertical-wheel bioreactors. The transcriptomic profile of cerebellar organoids derived under dynamic conditions demonstrates a faster cerebellar differentiation combined with significant enrichment of extracellular matrix and upregulation of transcripts involved in angiogenesis when compared with the static protocol. The authors anticipate that large-scale production of cerebellar organoids may help developing models for drug screening, toxicological tests and studying pathological pathways involved in cerebellar degeneration.

Six iBB researchers are among the most cited top scientists at the top 2% of their areas. Portugal is represented in this list compiled by Stanford University with 385 scientists affiliated to national institutions. The rankings are based upon a researcher’s citations for both a single year (2019) and cumulative across their careers. Titled “Updated science-wide author databases of standardized citation indicators,” the list uses algorithms that quantify and systematically rank individuals into consistent scientific fields. The scores are provided  with and without self-citations to lessen the impact of self-citations or the use of citation farms (small clusters of researchers massively citing each other’s work). Ranked within the careerlong citation impact list are these iBB researchers: Joaquim Cabral, Isabel Sá-Correia, Mário Berberan Santos, Miguel Prazeres, Carla Carvalho, also along with Carina Crucho in the
2017 single-year citations list.

Cell-based therapies have been showing unprecedented therapeutic potential, already changing the landscape of medical care. Extracellular vesicles are nanoparticles naturally secreted by cells, which are important mediators of intercellular communication in our organism and are able to mediate therapeutic effects from their cells of origin. These vesicles can also be used as drug delivery vehicles to target multiple diseases. In a paper recently published in Frontiers in Cell and Developmental Biology, iBB researchers in collaboration with iMM Lisboa, CQE-IST and the companies PBS Biotech and AventaCell Biomedical, developed a new strategy for the robust and scalable production of extracellular vesicles from mesenchymal stromal cells, using bioreactors and an animal serum-free cell culture supplement. This strategy, developed within the frame of the PhD Program in Bioengineering of Miguel de Almeida Fuzeta, is a relevant step towards the large scale production of extracellular vesicles form different human tissue sources, which are promising tools for the development of new therapies against a variety of diseases, from cardiovascular diseases to cancer.

In a new paper published in Frontiers in Bioengineering and Biotechnology, SCERG-iBB researchers in collaboration with colleagues from the Institute of Molecular Medicine (iMM) describe a novel differentiation strategy that uses defined medium to generate Purkinje cells, granule cells, interneurons, and deep cerebellar nuclei projection neurons, that self-formed and matured into electrically active cells. This research is expected to result in better models for the study of cerebellar dysfunctions and represent an important advancement towards the development of autologous replacement strategies for treating cerebellar degenerative diseases.

Type 1 diabetes is an auto-immune disease where patients need to monitor and take insulin daily. Transplantation of encapsulated islet cells is performed in some countries to restore glucose control, but shortage of donors is a major bottleneck. Devices with stem cell-derived beta cells are now in clinical trials. Researchers at SCERG-iBB and Harvard Medical School performed an early health technology assessment modeling study to simulate, based on bioprocess and disease progression modeling, the manufacturing costs of devices containing pluripotent stem cell (PSC)-derived beta cells. This information was combined with medical data to determine cost-effectiveness of the new therapy. The work was published in Biotechnology Journal.

Human morphogenesis is a complex process involving distinct microenvironmental and physical signals that are manipulated in space and time to give rise to complex tissues and organs. The development of organoids represents a novel way to modeling such complexity. Advances in the bioengineering field have allowed the manipulation of different components, including cellular and noncellular factors, to better mimic the natural microenvironment and generate better organoid models of human morphogenesis. In a paper published in Stem Cells International, a team of researchers from the Stem Cell Engineering Research Group (SCERG) at iBB in collaboration with the Institute of Molecular Medicine reviewed the bioengineering strategies used to control the initial state and spatiotemporal positioning of cells within organoids and, lastly, the growth and remodeling of multicellular aggregates to achieve mini organ-like structures.

There is a high demand for functional bone grafts worldwide partly due to the increased life expectancy. Bone matrix proteins, especially osteopontin (OPN) and osteocalcin (OC), have been reported to regulate some physiological process, such as cell migration and bone mineralization. However, the effects of OPN and OC on cell proliferation, osteogenic differentiation, mineralization and angiogenesis are still undefined.  In a recent study published in Journal of Cellular and Biochemistry, researchers from SCERG-iBB working with colleagues from the Rensselaer Polytechnic Institute assessed the exogenous effect of OPN and OC supplementation on human bone marrow mesenchymal stem/stromal cells proliferation and osteogenic differentiation.  These results suggest that OC and OPN stimulate bone regeneration by inducing stem cell proliferation, osteogenesis and by enhancing angiogenic properties. The synergistic effect of OC and OPN observed in this study can be applied as an attractive strategy for bone regeneration therapeutics by targeting different vital cellular processes.

Cell-derived extracellular matrix (ECM) has been employed as scaffolds for tissue engineering. SCERG-iBB researchers working with colleagues from the Rensselaer Polytechnic developed bioactive cell-derived ECM electrospun polycaprolactone (PCL) scaffolds produced from ECM derived from human mesenchymal stem/stromal cells (MSC), human umbilical vein endothelial cells (HUVEC) and their combination based on the hypothesis that the cell-derived ECM incorporated into the PCL fibers would enhance the biofunctionality of the scaffold. The findings show that all cell-derived ECM electrospun scaffolds promoted significant cell proliferation compared to PCL alone, while presenting similar physical/mechanical properties. Additionally, MSC:HUVEC-ECM electrospun scaffolds significantly enhanced osteogenic differentiation of MSCs. The study was published in Materials Science and Engineering: C.