ORLOVA LAB

Pluripotent stem cells for vascular differentiation and disease modeling

 

RESEARCH

Blood vessels are essential for proper functioning of tissues and organs in our body, and vascular dysfunction is associated with many cardiovascular and neurodegenerative diseases. Insight into the  interactions between vascular cells and the local microenvironment are therefore key to understanding many different diseases.  Human induced pluripotent stem cells (hiPSCs) derived from patients with genetic vascular disorders can form blood vessel cells and provide human models for disease that can be used to find new therapeutics and strategies for disease prevention.

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DIFFERENTIATION OF HIPSCS

We utilize hiPSCs derived from healthy donors and patients with genetic vascular disorders. Over recent years, we have developed efficient protocols to differentiate different endothelial cell (EC) subtypes, pericytes, vascular smooth muscle cells, as well as myeloid cells, such as monocytes and macrophages. Specifically we investigate the generation of tissue-specific vascular cells with focus on the heart and brain vasculature.

VESSELS ON A CHIP

We trying to recreate both micro- and macrovascular- structures inside of microfluidic devices. For this we use modling approach to create tubes of around 100-150um in diameter and
self-organisation in microfluidic devices or chips, to create perfused micro-vessels on average 10-50um in diameter. Additionally, we are exploring photopatterning technologyto to recreate the same pattern repeatedly and thus eventually make micron-size self-organised structures of endothelial cell tubes.

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DISEASE MODELS

Using these 3D vessels on a chip and hiPSC from patients we aim to develop realistic disease models for hereditary hemorrhagic telangiectasia (HHT) and cerebral amyloid angiopathy (CAA), and model tumour angiogenesis and inflammation with patient-specific hiPSCs.

RNA-SEQ

Using CRISPR/Cas9 based gene targeting, we have generated several fluorescent reporter hiPSC lines for core transcriptional factors (TF) that are being used to advance our understanding of lineage specification and differentiation of ECs with different mesodermal origins and distinguishable by their core transcriptional signature.

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PEOPLE

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LISA VAN DEN HIL

Research Technician

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MEES DE GRAAF

PhD Student

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XU CAO

PhD Student

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OLEH HALAIDYCH

PhD Student

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DR. AMY COCHRANE

PostDoc

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DENNIS NAHON

PhD Student

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DR. MARC VILA CUENCA

PostDoc

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DHANESH KASI

PhD Student

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DR. VALERIA ORLOVA

Principle Investigator

 
 
 

de Graaf MSN, Cochrane A, van den Hil FE, Buijsman W, van der Meer A, van den Berg A, Mummery CL, Orlova VV. APL Bioengineering. 2019. 
doi: 10.1063/1.5090986

Cao X, Yakala GK, van den Hil FE, Cochrane A, Mummery CL, Orlova VV. Stem Cell reports. 2019.
doi: 10.1016/j.stemcr.2019.05.003

Halaidych OV, Mummery CL, Orlova VV. BBRC. 2019.
doi: 10.1016/j.bbrc.2019.03.143

Halaidych OV, Cochrane A, van den Hil FE, Mummery CL, Orlova VV. Stem Cell Reports. 2019.
doi: 10.1016/j.stemcr.2019.02.003

Halaidych OV, van den Hil FE, Mummery CL, Orlova VV. JoVE. 2018. doi: 10.3791/58678

Cochrane A, Albers HJ, Passier R, Mummery CL, van den Berg A, Orlova VV, van der Meer AD.
Adv Drug Deliv Rev. 2018 Jun 23. pii: S0169-409X(18)30146-7. doi: 10.1016/j.addr.2018.06.007.

Halaidych OV, Freund C, van den Hil F, Salvatori DCF, Riminucci M, Mummery CL, Orlova VV. Stem Cell Reports. 2018 May 8;10(5):1642-1656. doi: 10.1016/j.stemcr.2018.03.012.

Guadix JA, Orlova VV, Giacomelli E, Bellin M, Ribeiro MC, Mummery CL, Pérez-Pomares JM, Passier R.
Stem Cell Reports. 2017 Dec 12;9(6):1754-1764. doi: 10.1016/j.stemcr.2017.10.023.

Giacomelli E, Bellin M, Sala L, van Meer BJ, Tertoolen LG, Orlova VV, Mummery CL.
Development. 2017 Mar 15;144(6):1008-1017. doi: 10.1242/dev.143438

Birket MJ, Ribeiro MC, Verkerk AO, Ward D, Leitoguinho AR, den Hartogh SC, Orlova VV, Devalla HD, Schwach V, Bellin M, Passier R, Mummery CL.
Nat Biotechnol. 2015 Sep;33(9):970-9. doi: 10.1038/nbt.3271

Orlova V, Mummery C.
Cell Stem Cell. 2016 Mar 3;18(3):422. doi: 10.1016/j.stem.2016.02.013

Passier R, Orlova V, Mummery C.
Cell Stem Cell. 2016 Mar 3;18(3):309-21. doi: 10.1016/j.stem.2016.02.011. Review

Orlova VV, van den Hil FE, Petrus-Reurer S, Drabsch Y, Ten Dijke P, Mummery CL.
Nat Protoc. 2014;9(6):1514-31. doi: 10.1038/nprot.2014.102

Orlova VV, Drabsch Y, Freund C, Petrus-Reurer S, van den Hil FE, Muenthaisong S, Dijke PT, Mummery CL.
Arterioscler Thromb Vasc Biol. 2014 Jan;34(1):177-86. doi: 10.1161/ATVBAHA.113.302598

van der Meer AD, Orlova VV, ten Dijke P, van den Berg A, Mummery CL.
Lab Chip. 2013 Sep 21;13(18):3562-8. doi: 10.1039/c3lc50435b

Contact Dr. Valeria Orlova
Department of Anatomy and Embryology
Leiden University Medical Center
The Netherlands

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