Cardiac regeneration with cell therapy, from theory to practice
In cases where patients have suffered an acute myocardial infarction with significant damage to the cardiac muscle, the only path towards recovery is through a heart transplant. Although the technique is well known, 50% of all transplant patients die in the following 10 years and only 20% are still alive 20 years later. Thus, heart transplants can't be considered the best solution to treat severe heart damage.
Regenerative medicine (methods that combine cell therapy with materials to improve biological functions) holds promising solutions to treat heart disease, but the lack of uniformity and agreement on methods used make it difficult to compare results obtained in the laboratory.
During the scientific debates Unsolved Problems in Heart Repair held by B·Debate and the Vall d’Hebron Research Institute (VHIR) from 28 to 30 November at CosmoCaixa Barcelona, more than 30 national and international experts discussed basic research in cell therapy to regenerate the myocardia, clinical studies being carried out to ensure that these therapies are safe and effective, and the ethical issues and modifications to the current legal framework needed to apply them generally.
The scientific leader for this event was Manuel Galiñanes, head of the Department of Cardiac Surgery at the Vall d’Hebron University Hospital and head of the VHIR Reparative Therapy of the Heart Research Group.
Various clinical studies have shown that when stem cells are inserted into a heart after a heart attack, cardiac function improves. What is not yet clear is the mechanism through which this improvement comes about. On one hand, it is possible that these cells take over the function of those that were damaged. On the other, this may lead to a paracrine effect with the implanted cells stimulating recovery of the cells in the affected areas.
Experts wanted to identify the types of cells that offer the best results. Bone marrow cells, as well as those from adipose and striated muscle tissue, could be good candidates. Those from umbilical cords and iPS (induced pluripotent stem cells from adult cells) also have their own pros and cons.
During the session led by Andre Terzic, director of the Mayo Clinic’s Center for Regenerative Medicine (United States), participants discussed the possibility that the most appropriate system is a mix of different cell types. It is important to regenerate the heart, but also to preserve pre-existing cells, as when new cells are introduced there is a paracrine effect through which those affected by the cardiac event recover part of their original activity.
One of the problems facing this therapy is that allogeneic cells (those from donors) inserted into the heart are eliminated by the patient’s immune system. There are genetic issues involved in this immune response (ABO, MHC-HLA and mHC).
Dominique Charron, president of the BiobancUSA Advisory Board, mentioned that measures must be taken to avoid this and we must remember that heart transplants have been preformed for some years now and tools have been developed to prevent rejection in this process.
According to Massimiliano Gnecchi, professor in the University of Pavia Department of Cardiology (Italy), in-vitro tests could be a good way to predict clinical and functional results of cell therapy in patients, before moving into the laboratory.
Bernardo Nadal-Ginard, the first person to promote the idea of the myocardia’s ability to regenerate, highlighted that if we want to regenerate a tissue, versus trying to heal it, we must deeply understand its biology. The aim of regenerating the myocardia must be to protect and stimulate endogenous stem cells already present in the heart.
Regarding the optimum moment for applying cell therapy in an animal model, Stefan Janssens, professor of Medicine at the University of Leuven (Belgium), said that the window of time is very narrow. Animal models that are being used currently show that once acute inflammation has occurred, the relationship between effort and improvement decreases notably.
They also discussed the importance of dosing and composition in cell therapy. The volume of cells varies depending on the size of the animals being used in the experiment. Differences in volume from one animal to another make it difficult to develop tests that can be compared and used to reach conclusions. One of the other topics of debate was that no population of stem cells that can be administered is homogenous.
The following reports include the most noteworthy declarations from the speakers:
- Report on debate held 29 November 2012 (in Spanish)
- Report on debate held 28 November 2012 (in Spanish)
You can also follow the debate on Twitter @BDebate with the tag #BDebate