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A collaborative research project led by NUI Galway researchers has achieved a major breakthrough in the harnessing of stem cells to generate patient-specific heart tissue in a dish for the treatment of heart disease and sudden death in young children.
This latest advanced stem cell study achieved by the Irish-based research team is crucial in the diagnosis and treatment of genetic cardiac conditions.
It is the first case in Ireland of synchronised beating heart cells being created from human pluripotent stem (iPS) cells.
IPS cells are stem cells created from adult cells that can be reprogrammed to develop into any type of cell in the human body.
Stem cell research into heart conditions has increased substantially in recent years having revolutionised our understanding of the heart’s mechanical and electrical communication, coordination and function.
Reprogramming cells using CRISPR
Because mature human heart cells cannot be grown outside the body under normal conditions, and any alternative would potentially harm the at-risk patient, stem cells can be used to create a skin biopsy sample from a particular patient and those same skin cells can be engineered into heart cells.
By ‘reprogramming’ these newly-created cells, researchers can then create an exact replica of that patient’s heart tissue in a laboratory dish.
Aside from not putting the patient at risk, these newly-generated heart cells can be a testing ground for new medicines and their effectiveness in preventing arrhythmias.
On a similar note, a genetic defect in the heart cell can be repaired through CRISPR/Cas9 genome editing and this repaired heart cell can be then directly compared to the diseased heart cell in the lab.
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Dr Min Liu, postdoc researcher in stem cell biology, Biomedical Sciences Building at NUI Galway. Image via Aengus McMahon
Deep analysis of Long QT syndrome
This major breakthrough in Irish stem cell research was a collaborative effort from the CÚRAM centre in NUI Galway, the Regenerative Medicine Institute (REMEDI) and Our Lady’s Children’s Hospital Crumlin (OLCHC), with this particular study initiated by REMEDI’s director and co-principal investigator at CÚRAM, Prof Timothy O’Brien, and Our Lady’s Children’s Hospital Crumlin consultant paediatric cardiologist Dr Terence Prendiville.
With the ability to now properly analyse damaged heart cells, the researchers are now working with adult and paediatric cardiologists to help define the burden of Long QT syndrome – an inherited rhythm disease – in affected families and develop technologies to measure the effectiveness of therapies and genetic repairs.
To that end, for the next phase of this study, researchers are seeking families affected by Long QT Syndrome to come forward for a skin biopsy or consultation with their doctor.
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Prof Timothy O’Brien, director of REMEDI and co-principal investigator at CÚRAM in NUI Galway. Image via Aengus McMahon
Pushing the envelope on medical therapies
The aim is to recruit both affected and unaffected family members to better understand what places one family member at risk and not another, preferably with the identified causative gene mutation in the family.
Once an established method for generating patient-derived heart tissue has been properly tested and confirmed, the same scientific technology will be used to explore other inherited arrhythmia conditions and cardiomyopathies.
Speaking of the major breakthrough, Dr Prendiville said: “I meet families every week in the hospital from all over Ireland who have been affected by the sudden unexpected death of a loved one.
“Their first question to me is: ‘Could this affect my child?’ Their next question is: ‘How do I keep them safe?’ Research such as this allows us to continue to push the envelope on developing medical therapies that safeguard against risk of sudden death.”
Genetic testing image via Shutterstock