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(BHF Acc) Injectable iPSC-cardiomyocyte/peptide hydrogel composites for cardiac repair


Project Description

iPSC-based cell therapies have shown promise in regeneration of the heart following MI1. iPSC may become the source of choice of autologous cardiomyocytes as they have (1) a reduced risk of immune rejection and (2) have the capacity to be extensively expanded thereby enabling the production of large number of cardiomyocytes for cardiac repair. However, the survival, engraftment and retention of implanted iPSC-cardiomyocytes in the heart remain a major problem. It has been shown that stem cells display low survival and viability when transplanted into the damaged myocardium. This is likely due to the challenging environment ischaemia generates for the implanted cells with low oxygen supply, inflammation and lack of extracellular matrix and supporting cells2. This project will address this challenge by developing an engineered iPSC-cardiomyocytes - peptide hydrogel injectable composite scaffold that promotes the retention and survival of the cells at the targeted site.
The project has two aims:
1) To generate optimized hydrogel/iPS-cardiomyocytes composites. This aim includes hydrogel optimisation (i.e. mechanical properties and functionality), the development of the 3D culture system of iPSC-cardiomyocytes/hydrogels, and the phenotype characterisation of the iPSC-cardiomyocytes including survival, proliferation rate, maturation, and contractile function (Year 1)
2) To test the regenerative capacity of the peptide hydrogel/iPS-CM composites in repairing infarcted myocardium in vivo. We will develop a rat model of MI. Following infarction, rats will be divided into three groups: i) receiving peptide hydrogel/iPS-cardiomyocytes composites; ii) receiving peptide hydrogel only; iii) receiving medium only. Cell survival, cardiac function and infarct size will be evaluated using a fluorescent cell tracker, echocardiography and histology respectively at 4 weeks after infarction. (Year 2-3)
It is expected that this project will provide novel insights in the area of cardiac cell based therapy and in the use of iPSC-cardiomyocytes - peptide hydrogels composites to improve cardiac tissue regeneration and recovery after MI by improving cell retention and engraftment at damaged site.

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants are expected to hold, or about to obtain, a minimum upper second class undergraduate degree (or equivalent) in a biological/medical sciences subject or in material sciences/biomaterials. A Masters degree in a relevant subject and/or experience in material sciences/biomaterials is desirable.

Applications are welcome for entry points in April 2020 or September 2020. Please select the appropriate entry point when applying.

Funding Notes

This project is to be funded under the BHF Accelerator Award. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BHF Accelerator Award website View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

1. Lalit PA, Hei DJ, Raval AN, Kamp TJ. Induced pluripotent stem cells for post-myocardial infarction repair: Remarkable opportunities and challenges. Circ Res. 2014;114:1328-1345
2. Robey TE, Saiget MK, Reinecke H, Murry CE. Systems approaches to preventing transplanted cell death in cardiac repair. J Mol Cell Cardiol. 2008;45:567-581

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