Stem cells that “learn” to differentiate. Gene therapies to improve the treatment of many heart diseases. The future of cardiology passes through cellular therapies. “In advanced heart failure and refractory angina, more severe forms of ischemic heart disease that due to their degenerative nature are no longer manageable by traditional drugs and technologies such as coronary artery bypass grafting and stenting, cell therapy has the ability to regenerate the tissues of the heart, restoring its function – he explains Giulio Pompilioscientific director of the vascular biology and regenerative medicine unit of the Monzino cardiology center – Cell therapy involves the use of induced pluripotent stem cells (induced pluripotent stem cells o iPS), that is to say mature stem cells that are genetically reprogrammed in the laboratory to make them ‘regress’ to the embryonic stage and then differentiate, i.e. made capable of transforming themselves into the tissues of which repair is to be obtained, in this case into cardiac muscle cells or cardiomyocytes . These cells are then reinfused into the heart to restore contractile capacity to the heart or improve the blood supply to the heart tissue. “
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Personalized medicine
Stem cell therapies represent one of the most advanced examples of personalized medicine. Autologous progenitor cells (ie from the patient himself) are used. The most promising ones from which to start to obtain the IPS are the mesenchymal ones. They reside within not only the bone marrow but also most connective tissues: peripheral blood, skeletal muscle, adipose tissue, tendons. A recent international study has shown that the use of IPS stem cells derived from smooth muscle tissue (that of the heart and vessels) improves ischemia and promotes the genesis of new blood vessels. But that’s not enough. Stem cells have also been used for tissue engineering applications of vessels. In recent times, research has made great progress thanks to the ability to produce 3D stem-derived organoids. In the field of cardiovascular research, 3D cell culture systems, such as human organoids, closely mimic the complex in vivo physiology of the vascular system, enabling the study of the genetics, function and pathophysiology of the disease.
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The secrets of cells
“The IPS cells taken from the patient’s blood – continues Pompilio – also have the property of being little recognized by the immune system, which makes them at a lower risk of rejection. Lately, thanks to this characteristic, the industry is trying to transform this autologous therapy in allogenic, that is with donors other than the patient himself. This aspect would allow a simpler industrial development because we move to a therapy that can be provided to the patient without having to submit him to the path of self-donation, a therapy defined ‘on the shelf’ that is over the counter. Furthermore, anti-rejection therapy does not seem necessary precisely because these cells are ‘immune-privileged’, little recognized by the immune system. A recent trial, one of the largest that ended last year and which studied mesenchymal cells allogeneic – hence from donor – on patients with heart failure, confirmed the absence of rejection or advanced cell therapy is a demonstration of what the future of cardiac cell therapy could look like. “
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Gene therapy, beyond genetic pathologies
Another example of possible application of advanced therapies is that of gene therapy, that is the possibility of carrying a gene at the level of DNA but also of RNA to replace a missing or altered function. “For some very serious genetic diseases, such as conduction system diseases that lead to heart rhythm disturbances or genetic diseases associated with a weakening of the heart’s ability to contract or cardiomyopathies, cardiovascular gene therapy is being investigated experimentally. But not only that. Gene therapy can not only be applied to genetic diseases, but there are also very interesting trials underway, internationally, which use DNA and RNA to treat the degenerative heart diseases mentioned above and treated with therapy. mobile phone ”, adds Pompilio.
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Collaboration between research, industry and institutions
In order for these therapies to become successful in the future and to be widely introduced, they need to be developed by industries in the sector. As with similar therapies, just think of CAR-T cells in oncology, or gene therapy for rare genetic diseases. “Cardiology is far behind, compared to other areas – concludes Pompilio. – My hope is that there will be a collaboration at the national level of the most important components that deal with advanced therapies: from the Academy, to laboratories, to institutions, to industries, also facilitated by PNRR funds. It is also important to establish partnerships between research and industrial development, between public and private sectors, the only way for therapies of this type, for such sophisticated technologies, to give them a future and sustainability, as has happened in other areas of medicine “.