Engineering vascularised tissue-specific disease models
Microvessels are our earliest functional organs, and their dysfunction is linked to numerous diseases. The Haase group focuses on the development of novel in vitro human assays for examining the pathology of vascular disease, with a particular focus on those related to endocrine disorders and genetic differences stemming from sex. Our group has expertise in generating perfusable 3D in vitro vascular models. By incorporating self-assembled microvessels with tissue-specific cells, our capillary systems are used to investigate vasculogenesis (vessel formation) as well as microvascular pathologies. Our interdisciplinary group employs engineered platforms to investigate the role of physiological and pathological levels of mechanical cues on vascular development.
As tissue engineers, we employ a variety of fabrication, microscopy and biological techniques to ultimately increase our understanding of complex vascularised tissues. Our group will work closely with clinicians and experts in modelling to develop physiological platforms for practical and predictive uses.
The Haase group develops strategies to vascularise organoids, spheroids and tissue grafts, with a particular focus on cardiac tissues. A long-term goal of the lab will be to implement our vascularised platforms for preclinical use.
Our group will generate scalable human vasculature using cells derived from induced pluripotent stem cells (iPSCs). By fusing perfusable capillaries with larger vessels we aim to form complete arteriole-capillary and capillary-venule connections in vitro. This work will involve microfluidic platform development and integrated actuation, as well as differentiation of human iPSCs. We will explore effects of vasodilation and re-circulating flow on-chip.
One of our aims is to vascularise tumour spheroid and organoid systems to develop physiological drug screening platforms. Integrating vasculature with iPSC-derived spheroid and organoid cultures (from healthy and diseased sources) will facilitate investigation of heterotypic cell interactions, physiologically relevant drug dissemination, and prolonged culture of microtissues. Our work will involve significant characterisation of microvessels and surrounding matrix, using tools such as atomic force microscopy (AFM) and mass spectrometry. Our long-term goal will be to use these systems for interrogation by targeted antibodies and small molecules.
One focus will be to exploit mechanical cues to promote iPSC differentiation and the development of mature cardiac tissue constructs. Compressive/tensile strains will be used to direct early cardiomyocyte differentiation in 3D. We will assess and manipulate cardiac function using electrical and mechanical forces. Strategies will be employed to form thick vascularised cardiac patches.
EMBL’s site by the sea completed its fifth year of operations. We look back at some key milestones and achievements since 2017.Edit
EMBL’s site by the sea hosted a trio of conferences this summer, covering topics ranging from vascular biology to engineered living systems to evolution.Edit
A new model could serve as a platform to investigate critical placenta barrier phenomena, including defence against bacteria, viruses, and parasites.Edit
Kristina Haase brings an engineer’s perspective to vascular disease and regenerative medicineEdit