Signalling mechanisms to maintain and repair human cardiac cells.
Research type
Research Study
Full title
Signalling mechanisms acting to maintain and repair human cardiac cell populations.
IRAS ID
200339
Contact name
Andrew J. Smith
Contact email
Sponsor organisation
University of Leeds
Duration of Study in the UK
2 years, 11 months, 30 days
Research summary
Heart failure is an already-large and growing clinical problem, a complicated disease driven by distinct signals in different heart cells, ultimately causing loss of heart muscle cells (cardiomyocytes). To treat heart failure, we must better understand how to manipulate signalling mechanisms in the heart, to reduce the loss of cardiomyocytes. The heart has self-repair capacity, but the cardiac stem cells capable of this are suppressed by signals from other cells. A clear understanding of the signals in the human heart’s various cell populations provides the essential foundation for manipulating these to improve support and repair of the injured heart.
To achieve this, we require human cardiac tissue, from which we will obtain the cell populations of interest. This can be done using pieces of heart tissue normally removed and discarded during the process of cardiac surgery: this allows maximal scientific gain with no patient impact, who undergoes surgery as normal. Any patient undergoing such cardiac surgery at the participating hospital could help this study, which will take place over three years, involving clinical researchers and a collaboration of scientists with expertise in all cardiac cell types.
Extensive information has already been collected from animal cell studies, but the essential next stage is translating this work into human cells. To provide comprehensive understanding, we will isolate each cell type, characterising signalling pathways and how these affect cell functions, and how these act on other cell populations. Firstly we will determine and manipulate the signals driving human cardiac stem cells to repair the heart by generating new blood vessels and supporting injured cardiomyocytes. We shall then examine the signalling mechanisms of supportive cells (cardiac fibroblasts) influencing stem cell functions and repair abilities. Thirdly, we will examine how cardiomyocyte signals are altered with disease and can be directly manipulated to aid cell functions.
REC name
Wales REC 1
REC reference
17/WA/0314
Date of REC Opinion
10 Oct 2017
REC opinion
Further Information Favourable Opinion