Cardiac Tissue Engineering: regeneration of the wounded heart
This paper summarizes recent research on the regeneration of hearts damaged by myocardial infarction. Due to a lack of heart donors and complications associated with immune suppressive treatments, new solutions are needed to regenerate hearts damaged by myocardial infarction. One method for regenerating functional myocardial tissue is cell grafting by syringe injection directly in the ventricular wall or coronary vessels. So far adult stem cells such as bone marrow stem cells have been studied by several teams who claim these cells can develop into cardiomyocytes. Most studies support the notion that cell engraftment in animal models of myocardial infarction can improve contractile function (although the mechanism behind this functional improvement is not clear). The paper goes on to say that cell engraftment is very inefficient, and that 90% of the cell suspension injected is lost and does not engraft. Therefore more effort is going into the development of tissue engineering strategies using biomatrices to successfully engraft new cells into the myocardium. Researchers quickly realized the material had to be elastic to compensate for the heart’s changing shape. Currently several groups are working with scaffold materials composed of natural polymers such as collagen (a major constituent of the cardiac ECM), which have shown promising results. One of the most recent approaches involves the use of materials to create electrically communicating 3D cardiac tissue layers. In order to do this, cells are adhered on tissue culture plates previously coated with poly(N-isopropylacrylamide) (PIPAAm), a temperature sensitive polymer. At high temperatures the polymer is hydrophobic, enabling cell adhesion, but at lower temperatures it is hydrophilic, and becomes inappropriate for cell adhesion due to rapid hydration and swelling of the polymer. Eventually, the matrix can be grown into as many as four layers of synchronously beating cardiomyocytes, which can then be implanted into rats with induced myocardial infarction. The implanted rats show improved myocardial contractility and increased vascularization of the area.
4 comments:
Two questions: a) You mentioned they were able to make cells adhere via temperature-sensitive cells, but how do they target cells on a small specific region of the heart? b) Do they mention anything about removing/regenerating the dead tissue from an infarction, or do these implants just build over the dead tissue?
Heart formation is a very complex process, and the fact that 90% of injected cell suspension cannot be maintained just shows how far off we are from creating a working heart scaffold. I think more should be done to understand the process of heart regeneration before putting work into trying to create these implants.
It's true that hydrophobic materials promote protein and cell attachment, but they also promote protein spreading. Spreading can change the properties of adhered proteins so much that the proteins are no longer recognized by the body and can cause an immune response. I wonder what has been done to minimize spreading and inhibit the immune response.
It seems like everyone is doing research on generating biosynthetic heart. I'm just wondering how long can the implanted rats maintain the improved myocardial contractility and increased vascularization of the area?
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