The Stem Cell Biotechnology group will contribute for the thematic strand Molecular and Stem Cell-Based Therapies. The objectives of Stem Cell Biotechnology group for 2015-2020 are summarized in 4 points:
1- CELL REPROGRAMMING: the development of strategies for efficient cell reprogramming of somatic cells into hematopoietic stem cells (HSCs) and cardiac cells (CRDH and BSCBT sub-groups). The objective is supported by funds of NIH, FCT (PTDC/SAU-ENB/113696/2009; PTDC/CTM-NAN/120552/2010) and an ERC starting grant (project 307384). In case of cell reprogramming of human somatic cells into HSCs, we will build our approach in the results recently reported by us in mouse cells (Pereira et al., Cell Stem Cell 2013). In addition, we will investigate the mechanisms that mediate the human hemogenic reprogramming process. In case of cell reprogramming of somatic cells into cardiac cells, we will develop triggerable systems that allow precise control of timing, duration, magnitude and spatial release of the transcription factors either in vitro or in vivo. This objective is in line with the work that we have performed in the last 5 years in which we have demonstrated the differentiation mechanism mediated by polymeric nanoparticles within stem cells (Maia et al., ACS Nano 2011, Santos et al., ACS Nano 2012 and 2013).
2- STEM CELL MODULATION: the development of strategies to modulate stem cell engraftment and stem cell differentiation (CSC, SCM, SCDS and BSCBT sub-groups). The objective is supported by funds of FCT (PTDC/CTM-NAN/120552/2010; PTDC/BIM-MED/1118/2012; PTDC/CTM-NAN/119184/2010), QREN program (project stemcellbiotech), an ERC grant (project 307384) and a Marie Curie ITN (project reference: 289454). Because most of stem cell-based therapies being evaluated in pre-clinical and clinical trials for the treatment of several diseases have poor engraftment, we aim at developing drug-based approaches to improve the grafting of stem cells. Another objective is to identify drugs and nanomaterials for the controlled release of drugs to differentiate cancer stem cells. The goal here is to develop nanoformulations that can specifically target cancer stem cells (blood and neural tissue) while allowing tissue stem cells to normally develop, based in the differences signatures of the cells (Castelo Branco et al., Clin Cancer Res 2011).
3- DRUG SCREENING: the development of stem cell–based assays and in silico approaches for drug screening and toxicity assessment (CRDH and BSCBT sub-groups). The objective is supported by contract research with companies, FCT (PTDC/SAU-TOX/121887/2010; EXPL/DTP-FTO/0570/2012) and a QREN grant (project stemcellbiotech). In the last 5 years, we have developed a blood vessel on a chip from human inducible pluripotent stem cells (iPSCs) to screen compounds that interfere with embryonic vascular development and we have generated an in vitro human blood brain barrier (BBB) model from hematopoietic stem cells relevant for drug discovery programs related to CNS diseases (both manuscripts submitted; technology being commercialized to big Pharma). During the next 5 years we aim to use that models to identify nanomaterials that can cross the BBB or blood vessels or have BBB/blood vessel toxicity. Moreover, we want to extend our expertise in the design of in vitro systems to screen drugs with therapeutic relevance for cardiovascular diseases and therefore we will develop a human cardiac tissue from iPSCs.
4- CLINICAL APPLICATIONS: development of new advanced methodologies based in stem cells to heal chronic non-healing wounds in diabetic patients or to regenerate myocardium after infarction (SCDS and BSCBT sub-groups). The objective is supported by contract research with companies (Crioestaminal) and FCT (EXCL/DTP-PIC/0069/2012). In collaboration with Associação Protectora de Diabéticos (APDP), we aim at evaluating the regenerative potential of stem cells in chronic diabetic wounds.