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SELECTBIO Conferences Bioengineering for Building Microphysiological Systems 2022

Valeria Orlova's Biography

Valeria Orlova, , Leiden University Medical Center

Dr. Orlova is recognised for her research on hiPSC applications to cardiovascular biology, disease modelling and blood vessels in organ-on-chip devices. She has a strong background in vascular biology with expertise that includes differentiation of endothelial cells, pericytes, vascular smooth muscle cells and inflammatory cells from hPSCs, assays for functional chararcterization of hPSC-derived vascular cells (inflammatory responses, barrier function, high-content intracellular Ca2+ release), photopatterning technology to design cell substrates, RNAseq and methods for 3D analysis of hiPSC-EC vessels in OoCs. Orlova coordinates a large interdisciplinary consortium funded by the Dutch Research Agenda: Research on Routes by Consortia (NWA-ORC 2019) in which ‘organ-on-chip' models for the lymphatic and immune system are being built using hiPSC as a precision tool to investigate immune system-related disorders.

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Tuesday, 25 October 2022 at 10:00

Add to Calendar ▼2022-10-25 10:00:002022-10-25 11:00:00Europe/London3D VESSELS-ON-CHIP TO MODEL VASCULAR DISEASE AND BEYONDBioengineering for Building Microphysiological Systems 2022 in Rotterdam, The NetherlandsRotterdam, The

Small vessel diseases are the leading cause of disability and death worldwide. The major challenge is that they are multisystem disorders affecting different organs, such as the brain, heart and kidney.  They have been difficult to model in vitro because high-quality vascular cells are difficult to derive from patients and the local organ microenvironment which is difficult to mimic often contributes to the disease. For this reason, human induced pluripotent stem cells (hiPSCs) have become attractive sources of patient- and organ-specific cells. We use hiPSCs to re-create blood vessels on microfluidic chips that recapitulate micro- and macrovascular networks and the local microenvironment. We developed efficient protocols to differentiate hiPSCs towards ECs, pericytes/vSMCs, and inflammatory cells (monocytes and pro- and anti-inflammatory macrophages).  We have demonstrated that both micro- (10-50 µm) and macro-scale (250-300 µm) perfusable 3D vessels composed of hiPSC-derived endothelial cells, pericytes/vSMCs, and other non-vascular components, such as hiPSC- derived astrocytes, can be generated inside the microfluidic devices. Recently we also developed a microphysiological system that behaves as a human “mini-heart” using cardiomyocytes, endothelial cells, and cardiac fibroblasts all derived from hiPSCs. These mini-hearts can be produced just 5000 cells and without specialized equipment.  They thus represent a low-cost, low tech platform for cardiac drug discovery and disease modeling. Using isogenic patient hiPSC lines and 3D vessels-on-chip, we recapitulated the phenotype of a genetic vascular disease called hereditary hemorrhagic telangiectasia (HHT). This patient-based hiPSC model serves as proof of principle that vascular diseases can be modeled using patient-specific hiPSCs in 3D microfluidic chips and used to identify new target cells and possible pathways for therapy.

Add to Calendar ▼2022-10-24 00:00:002022-10-25 00:00:00Europe/LondonBioengineering for Building Microphysiological Systems 2022Bioengineering for Building Microphysiological Systems 2022 in Rotterdam, The NetherlandsRotterdam, The