Engineering a Cardiovascular Tissue Graft from Human Embryonic Stem Cells
Cardiovascular disease (CVD) affects more than 71 million Americans and 1.7 million Californians. Recently, engineered cardiovascular tissue grafts, or patches, including one made from mouse embryonic stem cells (ESC), have shown promising results as a future therapy for CVD. Our overall goal is to extend these recent results to human ESC as follows.
Aim 1: Apply mechanical stretch and electrical pacemaker-like stimulation to hESC-derived heart cells in order to make them stronger and beat at the same time.
Current methods to turn hESC into heart cells do not result in the organization required to generate enough strength to support a weak heart and to avoid irregular heart beats. We will use specially engineered devices to apply mechanical stretch and electrical pacemaker-like stimulation to hESC-derived heart cells in order to strengthen them and make them beat in unison.
Aim 2: Engineer a cardiovascular patch from hESC-derived heart cells in order to make a potential new therapy for heart disease.
Recently, heart cells from mouse ESC, supporting structures called scaffolds, and mechanical stretch have successfully been combined to engineer a cardiovascular patch. We will combine the hESC-derived heart cells from Aim 1, scaffolds, and the same stretch and pacemaker-like stimulation as in Aim 1 to engineer a cardiovascular patch. In addition, we will add a specialized substance called VEGF to our patch so that, potentially, a blood supply will form around it after it is implanted on a diseased heart. We believe a blood supply will be necessary to keep our patch healthy, and in turn, this will allow our patch to help a damaged heart pump better.
Aim 3: Assess whether our patch can remain healthy and also strengthen the heart of a rat after it has undergone a heart attack.
We will first implant our cardiovascular patch in the rat aorta, the main blood vessel that supplies blood to the body, to test whether the patch remains healthy and whether it can contract and beat on its own. We will first use the aortic position because we feel it will allow us to assess the inherent fu