Modeling Rett Syndrome With Human Patient-Specific Forebrain Organoids
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.
Stem cell Manufacturing and Artificial Intelligence-based Modeling
The project "SMART:New technologies and strategies for Stem cell Manufacturing bioprocess monitoring and ARTificial intelligence-based modeling" has been recommended for funding by FCT (2020 Call for SR&TD Project Grants). The goal of SMART is to develop new monitoring and modeling strategies envisaging more efficient bioreactor-based processes for the manufacturing of human induced Pluripotent Stem Cell-derived cardiomyocytes for biomedical applications, using artificial intelligence to integrate bioprocess monitoring data with biological data. The project, which falls within the scientific area of Chemical Engineering, is headed by Carlos Rodrigues from SCERG-iBB.
Regeneration of Periodontal Tissues with Hierarchical Biomimetic Scaffolds
The project "DentalBioMatrix: Exploiting the power of decellularized extracellular matrix to fabricate hierarchical biomimetic scaffolds to regenerate functional periodontal tissues" has been recommended for funding by FCT (2020 Call for SR&TD Project Grants). The goal of DentalBioMatrix is to develop novel bioengineering strategies to regenerate periodontium, by engineering hierarchically designed compartmentalized systems to meet the different characteristics of the tissues involved in periodontal defects. Decellularized extracellular matrix (dECM) will be used to create complex dECM-derived scaffolds to recreate the different niches of periodontium. Collectively, this approach will potentially provide the opportunity to harness the properties of periodontal tissue ECM, recreating a local niche at the tooth interface that can promote periodontal regeneration, especially important for osteoporotic and older patients with compromised ECM. The project, which falls within the scientific area of Medical Biotechnology, is headed by Marta Carvalho from SCERG-iBB.
Production of Extracellular Vesicles Derived from Mesenchymal Stromal Cells in Bioreactors
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, SCERG-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.
Tailored Cytokine Optimization for ex vivo Expansion of Human Hematopoietic Stem/Progenitor Cells
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.
From Human Pluripotent Stem Cells to 3D Cardiac Microtissues: Progress, Applications and Challenges
The knowledge acquired throughout the years concerning the in vivo regulation of cardiac development, has promoted the establishment of protocols to obtain cardiomyocytes (CMs) and other cardiac cells from human pluripotent stem cells (hPSCs). Among other developments in the field, the transition from homogeneous cultures of CMs to more complex multicellular cardiac microtissues (MTs) increased the potential of these models for clinically relevant applications such as drug screening, cardiotoxicity tests and for studying cardiac disorders in vitro. In a review paper recently published in Bioengineering by researchers from SCERG-iBB, it was addressed the state of the art of the generation of different cardiac cells from hPSCs and the impact of transitioning CM differentiation from 2D culture to a 3D environment. Additionally, current methods that may be employed to generate 3D cardiac MTs were reviewed and, finally, the adoption of these models for in vitro applications and their adaptation to medium- to high-throughput screening settings was also be highlighted.
This work used one of the most selective and high-affinity pairs found in Nature, avidin-biotin, to create affinity-triggered hydrogels. The multimerization of the biotin was studied by conjugation into different multi-arm polyethylene glycol molecules. Depending on the multimerization, assemblies with tuneable affinity constant were obtained leading to hydrogels with different mechanical properties and controllable erosion time and profiles. The results showed that mimicking natural multivalency gave rise to robust biocompatible hydrogel with applications in tissue engineering and stem cell research. The study results from ongoing collaboration between prof. Cecília Roque (FCT-NOVA) and prof. Tiago Fernandes (Técnico) and was recently published in the ACS journal “Biomacromolecules”.
An increased longevity is only justified with quality of life
SCERG director, distinguished Professor Joaquim Sampaio Cabral, talks about Regenerative Medicine and longevity to Jornal de Negócios. Read the interview (in Portuguese) by clicking on the title.
Conditioned Medium from Azurin-expressing MSC Demonstrates Anti-tumor Activity
Cell-based therapies can enhance the specificity of anti-cancer therapeutic agents. In this context, human mesenchymal stromal cells (MSC) hold a promising future as cell delivery systems for anti-cancer proteins due to their innate tropism for tumors. iBB researchers Marília Silva, Gabriel Monteiro, Arsénio Fialho, Nuno Bernardes and Cláudia Lobato da Silva, engineered human MSC through non-viral methods to secrete a human codon-optimized version of azurin (hazu), a bacterial protein with demonstrated anti-cancer activity towards different cancer models in vitro and in vivo. Upon treatment with conditioned media (CM) from these engineered cells, a decrease in cancer cell proliferation, migration and invasion was seen, and an increase in cell death was observed for breast and lung cancer cell models. The results achieved by SCERG- and BSRG-iBB researchers were published in Frontiers in Cell and Developmental Biology, Stem Cell Research section.
Medicine fights against aging disease
Joaquim Sampaio Cabral, director and founder of the Institute of Bioengineering and Biosciences, speaks of Regenerative Medicine, stem cells, anti-aging genes and 3D organ printing. Hear the podcast (in Portuguese) by clicking on the title.
SCERG researchers in collaboration with colleagues at the Institute of Molecular Medicine, iMM, have developed a protocol for the massive production of cerebellar organoids from human pluripotent stem cells. This capability opens up the possibility to modeling serious human cerebellar defects, like cerebellar ataxias, in vitro.
The role of Regenerative Medicine on Longevity
Next June 23 (Tuesday) at 4pm, Culturgest - Fundação CGD will host a virtual event dedicated to Longevity and Regeneration. Our coordinator Professor Joaquim M.S. Cabral will be talking about the "Role of Regenerative Medicine in Longevity". Don't miss!
Brain Organoids as Disease Models
Join the STEMCELL Brain Organoids Virtual Seminar on June 8th to hear our own Dr. Teresa Pereira da Silva talking about making cerebellar organoids.
Professor Joaquim M. Sampaio Cabral discusses Life Extension at the Antena 3 daily show "Prova Oral"
Joaquim M. Sampaio Cabral, Distinguished Professor, former Head of DBE, director of the Institute for Bioengineering and Biosciences, and principal Investigator of the Stem Cell Bioengineering reasearch group, at Técnico, has recently participated in the famous Antena 3 daily show "Prova Oral" to discuss the issues of "Life Extension". You can watch the full show (in Portuguese) by clicking on the title.
Allogeneic cell therapy products, such as therapeutic cells derived from pluripotent stem cells (PSCs), have amazing potential to treat a wide variety of diseases and vast numbers of patients globally. There are, however, various challenges related to the manufacturing of PSCs in the large quantities necessary to meet commercial needs. In a communication published in "Bioengineering", co-authored by Carlos Rodrigues, Teresa Silva and Professor Joaquim Cabral (SCERG-iBB), these challenges are addressed, presenting new scalable bioreactor technologies that can remove the bottleneck for large-scale manufacturing of high-quality therapeutic PSC-derived cells.
Human liver-based platforms hold great potential for clinical applications, disease modeling and drug screening. In a recent article published in Bioengineering, João Cotovio and Tiago Fernandes assess the production of the different hepatic cell lineages from human pluripotent stem cells (hPSCs), including hepatocytes, as well as the emerging strategies to generate hPSC-derived liver organoids, while highlighting current biomedical applications.
iBB Suspends Laboratory Activities in the Wake of the Covid-19 Crisis
Following the directives of the President of IST, from the 15th march on, and until further notice, the access to iBB research laboratories in both the Alameda and Taguspark campi is limited to the cleaning, security, maintenance of premises and equipment, and refilling of liquid nitrogen in containers. Research work in the labs is not authorized.
FCT Extends All Scholarship Contracts by One Month
Due to the exceptional measures decreed by the Government in the context of the Covid-19 pandemic, the Directive Council of the portuguese Foundation for Science and Technology (FCT) took the decision to automatically extend for one month the duration of all scholarship contracts. The measure is valid for all contracts funded by FCT that were in force on on the March 13, 2020. Click the title to learn more.
iBB Awarded with Grant to Explore Therapeutic Strategies for Angelman Syndrome
Evguenia Bekman and Tiago Fernandes from SCERG-iBB together with Simão Teixeira da Rocha from IMM-FMUL have been awarded by the Amélia de Mello Foundation (FAM) with the Pedro Maria José de Mello Costa Duarte Scholarship to carry out the project “Exploring new therapeutic strategies for Angelman syndrome: A disease modeling approach based on 3D cerebellar organoids derived from patient iPSCs”. The Angelman Syndrome is a genetic-neurological disease discovered in the 60s of the last century by the English pediatrician Harry Angelman, which is estimated to affect 1 in every 15,000 live births and which is characterized by developmental delay, difficulty in speech, sleep disorders, convulsions, disconnected movements and a frequent smile.
Maturation of Human Pluripotent Stem Cell-Derived Cerebellar Neurons in the Absence of Co-Culture
In a new research paper published recently 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.
ECM decorated PCL scaffolds for bone tissue engineering applications
In a recent work published in Journal of Biomedical Materials Research – Part B Applied Biomaterials, researchers from SCERG-iBB in collaboration with colleagues from the Rensselaer Polytechnic Institute (USA) and from the Centre for Rapid and Sustainable Product Development - Polytechnic Institute of Leiria, presented a method combining additive manufacturing techniques with cell-derived extracellular matrix to generate structurally well-defined bioactive scaffolds for bone tissue engineering.
Kartogenin-loaded coaxial PGS/PCL aligned nanofibers for cartilage tissue engineering
In a recent study published in Materials Science and Engineering C under the scope of PhD student João C. Silva thesis, researchers from SCERG-iBB in collaboration with colleagues from the Linhardt Labs (Rensselaer Polytechnic Institute, USA) developed and characterized coaxial poly(glycerol sebacate)/polycaprolactone aligned nanofibers able to promote the sustained release of a chondroinductive small mollecule (kartogenin).