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Cambridge Cardiovascular



Vascular smooth muscle cell development and disease

My group studies vascular development and vascular diseases such as aortic aneurysms and atherosclerosis. We have established new methods for generating human vascular smooth muscle cells (SMC) that originate from specific embryonic lineages, using directed differentiation of human embryonic and induced pluripotent stem cells (hESC & hiPSC).

Most recently, we have established an in vitro model for generating ESC-derived epicardium which we then use to generate ‘coronary’-like SMCs. We use these and other systems to study the molecular mechanisms that regulate vascular development. Using patient-derived iPSCs we also model genetic vascular diseases in which smooth muscle cells (SMC) are implicated, e.g. Marfan syndrome (FBN1).

My group is also investigating whether human pluripotent stem cell-derived cells may be used to regenerate the damaged heart, either by direct injection or by generating a vascularised next-generation tissue ‘patch’.  In particular we are interested in the role of the epicardium in regulating this regenerative response.


Key publications: 

Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration. Bargehr et al Nature Biotechnology 2019

Human Stem Cell-Derived Endothelial-Hepatic Platform for Efficacy Testing of Vascular-Protective Metabolites from Nutraceuticals. Narmada BC, Goh YT, Li H, Sinha S, Yu H, Cheung C. Stem Cells Transl Med. 2017 Mar;6(3):851-863.

An iPSC-derived vascular model of Marfan syndrome identifies key mediators of smooth muscle cell death. Granata A, Serrano F, Bernard WG, McNamara M, Low L, Sastry P, Sinha S. Nat Genet. 2017 Jan;49(1):97-109.

Embryological Origin of Human Smooth Muscle Cells Influences Their Ability to Support Endothelial Network Formation. Bargehr J, Low L, Cheung C, Bernard WG, Iyer D, Bennett MR, Gambardella L, Sinha S. Stem Cells Transl Med. 2016 Jul;5(7):946-59.

Vascular Smooth Muscle Cells in Atherosclerosis. Bennett MR, Sinha S, Owens GK. Circ Res. 2016 Feb 19;118(4):692-702.

Robust derivation of epicardium and its differentiated smooth muscle cell progeny from human pluripotent stem cells. Iyer D, Gambardella L, Bernard WG, Serrano F, Mascetti VL, Pedersen RA, Talasila A, Sinha S. Development. 2015 Apr 15;142(8):1528-41.

Embryonic origins of human vascular smooth muscle cells: implications for in vitro modeling and clinical application. Sinha S, Iyer D, Granata A. Cell Mol Life Sci. 2014 Jun;71(12):2271-88.

Directed differentiation of embryonic origin-specific vascular smooth muscle subtypes from human pluripotent stem cells. Cheung C, Bernardo AS, Pedersen RA, Sinha S. Nat Protoc. 2014 Apr;9(4):929-38.

Myocardin regulates vascular response to injury through miR-24/-29a and platelet-derived growth factor receptor-β. Talasila A, Yu H, Ackers-Johnson M, Bot M, van Berkel T, Bennett MR, Bot I, Sinha S. Arterioscler Thromb Vasc Biol. 2013 Oct;33(10):2355-65.

Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility. Cheung C, Bernardo AS, Trotter MW, Pedersen RA, Sinha S. Nat Biotechnol. 2012 Jan 15;30(2):165-73.

Professor in Cardiovascular Regenerative Medicine
Cambridge Lead for BHF Oxbridge Centre of Regenerative Medicine (CRM).
BHF Senior Clinical Research Fellow
Dr Sanjay  Sinha