Mechanobiological control of cardiac reprogramming
The human heart has a very limited (almost zero) capacity to regenerate following a heart attack, and most efforts in the field of tissue engineering/regenerative medicine are focused on the use of stem cells and tissue constructs to create functional chunks of heart muscle tissue for transplantation. Successful implementation of such an approach requires solving the vascularization challenge, a major focus of the CSET Lab. But what if it were possible to directly transform scar-forming cardiac fibroblasts into functional, beating cardiac myocytes? In fact, seminal work by other investigators has shown such an approach can partially restore heart function in mice after a heart attack. In this project, we are investigating the ECM's mechanobiological control of this transdifferentiation process, using a variety of experimental tools and platforms (i.e., engineered hydrogels, traction force microscopy, micropillar arrays, etc.) to do so.
Click photos above for a UM News Story about this project.
Video of mouse embryonic fibroblasts (MEFs) reprogrammed into beating cardiomyocyte-like cells. (Credit: Yen Kong)
Y.P. Kong, A.Y. Rioja, X. Xue, Y. Sun, J. Fu, and A.J. Putnam. “A Systems Mechanobiology Model to Predict Cardiac Reprogramming Outcomes on Different Biomaterials.” Biomaterials, 181:280-292 (2018).
Y.P. Kong, B. Carrion, R.K. Singh, and A.J. Putnam. “Matrix identity and tractional forces influence indirect cardiac reprogramming.” Scientific Reports, 3:3474 (Dec. 11, 2013).