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Institute for Bioengineering and Biosciences
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Participation in the EU Project FuturEnzyme

Participation in the EU Project FuturEnzyme | iBB | Scoop.it

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.

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Minicircle‐based Expression of VEGF in Mesenchymal Stromal Cells from Human Tissues

Minicircle‐based Expression of VEGF in Mesenchymal Stromal Cells from Human Tissues | iBB | Scoop.it

Mesenchymal stromal cells (MSC) have been exploited for the treatment of ischemic diseases given their angiogenic potential. A recent study published in the Journal of Gene Medicine by BERG and SCERG researchers compares the angiogenic potential of MSC obtained from bone marrow (BM), adipose tissue (AT) and umbilical cord matrix (UCM) that were genetically modified with VEGF‐encoding minicircle vectors. Transfected cells displayed higher in vitro angiogenic potential than non‐transfected controls, as demonstrated by functional in vitro assays, but no significant differences were observed among cells from different sources.

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Electrical Stimulation of Neural Stem Cells on Electroconductive Platforms Made of PEDOT:PSS

Electrical Stimulation of Neural Stem Cells on Electroconductive Platforms Made of PEDOT:PSS | iBB | Scoop.it

Many cells in the human body respond to electrical stimuli. The differentiation of neural stem cells into mature neurons, in particular, can be stimulated via electroconductive materials. In a recent publication in Frontiers in Bioengineering and Biotechnology researchers from SCERG-iBB and IT report on the electrical stimulation of neural stem cells on electroconductive platforms made of  conjugated polymer PEDOT:PSS. In a first stage, the performance of electroconductive platforms made of cross-linked (with GOPS or DVS) PEDOT:PSS was evaluated in terms of conductivity and stability. Three different protocols of electrical stimulation, with 3 different electrical currents (AC, DC and pulsatile DC), were then compared for neural stem cell differentiation. Results show that pulsatile DC assisted best in generating higher number of neurons. This finding is important for future regenerative approaches to treat neurological diseases and highlights the importance of using the correct platform to design scaffolds to regenerate the brain tissue.

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Modeling Rett Syndrome With Human Patient-Specific Forebrain Organoids

Modeling Rett Syndrome With Human Patient-Specific Forebrain Organoids | iBB | Scoop.it

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.

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Tailored Cytokine Optimization for ex vivo Expansion of Human Hematopoietic Stem/Progenitor Cells

Tailored Cytokine Optimization for ex vivo Expansion of Human Hematopoietic Stem/Progenitor Cells | iBB | Scoop.it

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.

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Development of Extruded Perfusion Bioreactor Platform for Cartilage Tissue Engineering

Development of Extruded Perfusion Bioreactor Platform for Cartilage Tissue Engineering | iBB | Scoop.it

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.

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The INMARE Legacy

The INMARE Legacy | iBB | Scoop.it

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. 

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Human Gut Microbiome Physiology Can Now be Studied In vitro Using Organ Chip Technology

Human Gut Microbiome Physiology Can Now be Studied In vitro Using Organ Chip Technology | iBB | Scoop.it

Studying direct interactions between the microbiome and intestinal tissue outside the human body represents a formidable challenge. A research team at Harvard’s Wyss Institute with SCERG-iBB researchers (Joaquim Cabral, Sasan Jalili-Firoozinezhad), has developed a solution to this problem using ‘organ-on-a-chip’microfluidic culture technology. The team is now able to culture a stable complex human microbiome in direct contact with a vascularized human intestinal epithelium for at least five days in a human Intestine Chip in which an oxygen gradient is established that provides high levels to the endothelium and epithelium while maintaining hypoxic conditions in the intestinal lumen inhabited by the commensal bacteria. The “anaerobic Intestine Chip” stably maintained a microbial diversity similar to that in human feces over days and a protective physiological barrier that was formed by human intestinal tissue. The study was published in Nature Biomedical Engineering.

 

Photo details: Bacteria of the human gut microbiome (yellow) are populating the intestinal epithelial channel of the anaerobic Intestine Chip. Credit: Wyss Institute at Harvard University.

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Stem Cell Manufacturing

Stem Cell Manufacturing | iBB | Scoop.it

The book "Stem Cell Manufacturing", edited by Joaquim Cabral, Cláudia Lobato Silva and Margarida Diogo from SCERG-iBB, together with Chase from Cellular Dynamics International, edited by Elsevier in 2016, continues to serve as a reference for Bioengineers involved in bringing stem cells frm the lab to the clinic and market. The book discusses the required technologies that enable the transfer of the current laboratory-based practice of stem cell tissue culture to the clinic environment as therapeutics, while concurrently achieving control, reproducibility, automation, validation, and safety of the process and the product.

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Compositional and Structural Analysis of GAGs in Cell-Derived ECM

Compositional and Structural Analysis of GAGs in Cell-Derived ECM | iBB | Scoop.it

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.

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Joaquim Cabral Elected Director of iBB

Joaquim Cabral Elected Director of iBB | iBB | Scoop.it

The Scientific Council of iBB has elected Joaquim Cabral for a new mandate as its Director. Alongside with the management of iBB, Prof. Cabral will continue to serve as the lider of the Stem Cell Engineering research group (SCERG). The election took place at the Alameda campus of IST on the 19th January 2019.

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Expansion and Harvesting Of Human Induced Pluripotent Stem Cells on Dissolvable Microcarriers

Expansion and Harvesting Of Human Induced Pluripotent Stem Cells on Dissolvable Microcarriers | iBB | Scoop.it

Development of efficient bioprocesses for human induced pluripotent stem cells (hiPSC) is critical for their medical and biotechnological applications. Scalable expansion of hiPSC is often performed using polystyrene microcarriers, which have to be removed using a time-consuming separation step. At the Stem Cell Engineering Research Group, novel xeno-free dissolvable microcarriers were applied for the first time for the integrated expansion and harvesting of hiPSC. After expansion, microcarriers were dissolved inside the bioreactor, allowing the recovery of more than 90% of the cells, which represents a significantly higher cell yield when compared with microcarrier filtration (45%). These results represent a major improvement for the downstream processing of hiPSC. Find more on the paper on Biotechnology Journal.

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Bioreactors for Stem Cell Expansion and Differentiation

Bioreactors for Stem Cell Expansion and Differentiation | iBB | Scoop.it

The book "Bioreactors for Stem Cell Expansion and Differentiation", edited by Joaquim Cabral and Cláudia Lobato Silva from SCERG-iBB has just been released by CRC Press. In the book, an international team of investigators presents thought-provoking reviews of bioreactors for stem cell expansion and differentiation and provides cutting-edge information on different bioreactor systems. The authors offer novel insights into bioreactor-based culture systems specific for tissue engineering, including sophisticated and cost-effective manufacturing strategies geared to overcome technological shortcomings that currently preclude advances towards product commercialization.

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Modeling Rett Syndrome with Human Pluripotent Stem Cells: Mechanistic Outcomes and Future Clinical Perspectives

Modeling Rett Syndrome with Human Pluripotent Stem Cells: Mechanistic Outcomes and Future Clinical Perspectives | iBB | Scoop.it

Rett syndrome (RTT) is a rare neurodevelopmental disorder caused by mutations in the gene encoding for the MeCP2 protein. Among different roles, MeCP2 has a high phenotypic impact during the different stages of brain development. Thus, it is essential to investigate the function of MeCP2 and its regulated targets. In a review paper published in the International Journal of Molecular Sciences, a team of researchers at SCERG-iBB provides a brief summary of the main neurological features of RTT and of the impact of MeCP2 mutations in the neuropathophysiology of the disease. A thorough revision of recent advances and future prospects of RTT modeling using human neural cells derived from pluripotent stem cells and its contribution for the current and future clinical trials for RTT is also provided.

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Transcriptomic Profiling of Human Pluripotent Stem Cell-Derived Cerebellar Organoids

Transcriptomic Profiling of Human Pluripotent Stem Cell-Derived Cerebellar Organoids | iBB | Scoop.it

 

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.

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Six iBB Researchers are Among the Most Cited Top Scientists in the World

Six iBB Researchers are Among the Most Cited Top Scientists in the World | iBB | Scoop.it

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.

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Production of Extracellular Vesicles Derived from Mesenchymal Stromal Cells in Bioreactors

Production of Extracellular Vesicles Derived from Mesenchymal Stromal Cells in Bioreactors | iBB | Scoop.it

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.

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Maturation of Human Pluripotent Stem Cell-Derived Cerebellar Neurons in the Absence of Co-Culture

Maturation of Human Pluripotent Stem Cell-Derived Cerebellar Neurons in the Absence of Co-Culture | iBB | Scoop.it

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.

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Transcriptomic Analysis of 3D Cardiac Differentiation of Human Induced Pluripotent Stem Cells

Transcriptomic Analysis of 3D Cardiac Differentiation of Human Induced Pluripotent Stem Cells | iBB | Scoop.it

Human induced pluripotent stem cells (hiPSCs) represent an almost limitless source of cells for biomedical applications including cardiomyocytes (CMs), the most predominant cell type in the human heart. iBB researchers have established an efficient and robust 3D platform for CM production from hiPSCs and studied the impact of 3D culture on CM differentiation and maturation compared with a 2D monolayer culture. It was found that CMs mature earlier and show an improved communication system in this 3D environment which was suggested to be responsible for a higher structural and functional maturation. This novel 3D culture platform and the CMs obtained can be used for disease modelling, drug screening and cardiotoxicity tests. The results were published in Scientific Reports.

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Towards Cost-effective Stem Cell-based Therapies for Type 1 Diabetes

Towards Cost-effective Stem Cell-based Therapies for Type 1 Diabetes | iBB | Scoop.it

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.

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Design Principles for Pluripotent Stem Cell-Derived Organoid Engineering

Design Principles for Pluripotent Stem Cell-Derived Organoid Engineering | iBB | Scoop.it

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.

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Synergistic Effect of Osteopontin and Osteocalcin on Stem Cell Properties

Synergistic Effect of Osteopontin and Osteocalcin on Stem Cell Properties | iBB | Scoop.it

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.

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Cell-derived Electrospun Microfibrous Scaffolds for Bone Tissue Engineering

Cell-derived Electrospun Microfibrous Scaffolds for Bone Tissue Engineering | iBB | Scoop.it

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.

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Francisco Moreira Defends PhD Thesis in Bioengineering

Francisco Moreira Defends PhD Thesis in Bioengineering | iBB | Scoop.it

Francisco Moreira has just defended his PhD thesis in Bioengineering (MIT Portugal) at Instituto Superior Técnico, wednesday the 12th December 2018 (14:00 H, room PA3). During the last years, and under the supervision of Joaquim Cabral and Cláudia Lobato Silva from SCERG-iBB, Francisco focused on the establishment of a scalable three-dimensional dynamic culture for the expansion of adipose tissue-derived MSC under xeno-free conditions. The title of his thesis is "Scalable Platform for the Expansion of Human Mesenchymal Stem/Stromal Cells Under Dynamic Conditions”.

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Diogo Silva Defends PhD Thesis in Bioengineering (Cell Therapies and Regenerative Medicine)

Diogo Silva Defends PhD Thesis in Bioengineering (Cell Therapies and Regenerative Medicine) | iBB | Scoop.it

Diogo Silva will be defending his PhD thesis in Bioengineering (Cell Therapies and Regenerative Medicine) at Instituto Superior Técnico, wednesday the 17th October 2018 (9:00 H, room 4.41). During the last years, and under the supervision of Joaquim Cabral from SCERG-iBB and Manuel Abecasis from IPO, Diogo developed new Chimeric Antigen Receptors (CARs) for various types of hematologic cancers and optimized existing CARs that are already in the clinic. The title of his thesis is "Engineering of T-Cells with Chimeric Antigen Receptors as a Therapy for Hematologic Cancers”.

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