We are engineering human stem cells to repair damaged hearts
In Greek mythology, Prometheus stole fire from Zeus and gave it to mankind. As punishment, Zeus had him chained to a rock where a great vulture tore at his liver every day. During the night, the liver grew whole again, only to have the vulture devour it again the next day.
Today, the regrowth of Prometheus' liver has become a symbol to medical researchers for the possible renewal of damaged human organs through the use of human stem cells.
Stem cells are characterised by their unique ability to constantly renew themselves and differentiate into a diverse range of other specialised cell types. In adults, stem cells act as a repair system for the body, replenishing specialised cells, and maintaining the normal turnover of regenerative organs such as blood, skin or intestinal tissues. Through medical research, stem cells can now be grown and transformed into a variety of specialised cells with characteristics consistent with tissues such as muscles or nerves.
Stem cell therapies already exist in medical practice. Bone marrow transplants have been used to treat leukemia and other blood malignancies for many years. But medical researchers hope to be able to use technologies derived from stem cell research to treat a much wider variety of diseases.
The question for us at University of Rome "Sapienza" in Italy is: Why not use stem cells to repair the human heart?
Several technologies have been described over the past 10 years to create functional heart tissue by using stem cells that have been isolated from other tissues such as bone marrow, skeletal muscle, and umbilical cord blood. But the benefits using these types of stem cells have ranged from marginal, to transient, to nil.
These cells are not cardiac cells. This means that they are not functionally programmed to work as cardiac cells in conjuction with the other resident cardiac cells. For this reason, our group has recently described and patented a method to obtain cardiac stem cells (CSCs) from small biopsies of myocardium and grow them through several generations in the laboratory without losing differentiation potential.
This means that CSCs represent a logical source for cardiac regeneration therapy because, unlike other adult stem cells, they are intrinsically programmed to generate cardiac tissue in the lab and thus increase cardiac tissue viability in humans. In addition, autologous CSCs can be employed without the ethical and immunological problems associated with the use of embryonic stem cells.
After injecting these cells into the hearts of animals with damaged myocardial tissue, my colleagues and I have observed an improvement in physiological functions. But we realized that cell transplantation may not always be suitable for catastrophic events, such as a heart attack in which there is major myocardial damage.
So we decided to use these stem cells in association with an artificial, netlike matrix to support formation of functional tissue-like structures that can be used in a new therapeutic approach to repair the heart.
Using a hybrid therapy that incorporates tissue engineering, we seeded a biodegradable mesh with cardiac stem cells. The mesh acted as a scaffold on which the stems cells were grown into morphologically recognizable cardiac tissue. We then joined the cardiac tissue built from the mesh scaffold onto the diseased structure of the heart to stimulate the regeneration of the optimal cell types for that particular portion of the heart.
In our case, ‘building a heart' requires the assembly of multiple functional units that include excitable and contractile ventricular myocardium and vasculature..
Using this technique in animals, the researchers have observed an increase in physiological functions such as the cardiac ejection fraction - a measure of the efficacy of the heart's contraction - and an improvement of cardiac chamber volumes following the placement of these tissue structures on the surface of the animal's damaged hearts.
These new transplantation systems enhance the viability of cells and stimulate their outward migration so that they can populate and help regenerate injured tissues.
Another field of application for this new technique may be myocardial reconstruction in pediatric patients. Instead of using synthetic materials to repair infant hearts, biological patches would grow concurrently with the physiological development of the child, making redo surgery unnecessary.
Another important issue is cost.
It is likely that the cost of this therapy will be considerably lower than standard transplantation procedures. The cost of surgery and the time of hospitalization would be reduced, and the standard use of life-long immune suppression medications would be unnecessary in the case of an engineered myocardium using a patient's own tissue. Unlike heart transplantation, this is a therapy that would not be exclusively reserved for wealthy, industrialised countries.
Myocardial tissue engineering may provide what we have so long sought: a Prometheus for modern times. (Giacomo Frati, Università di Roma La Sapienza, www.atomiumculture.eu)