Research identifies novel tissue-engineering biomaterials that enhance stemcell survival and engraftment in cardiac repair

Myocardial infarction (MI) is a leading cause of death in the United States. To study promising strategies for regenerating the damaged heart tissue post-MI, Mahmood Khan, PhD, MPharm, and his team of researchers examined the potential of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cardiomyocyte engraftment. Their findings, titled “Safety and Engraftment of Aligned Cardiac Patches Loaded with hiPSC-CMs in a Large Animal Model of Myocardial Infarction,” were recently published in Theranostics.  

In the past, engraftment after transplantation into ischemic myocardium has been a major barrier in cardiac patch and cell-based heart repair strategies. But in this work, the team developed a favorable safety profile that produced evidence of cardiomyocyte engraftment through: 

1. Reprograming human induced pluripotent stem cells into functional cardiomyocytes (hiPSCCMs) by developing a “cardiac patch” using a bi-layered, aligned coaxial patch for epicardial delivery of hiPSC-CMs in a preclinical porcine MI model. 
2. Fabricating the patch using polycaprolactone and gelatin via electrospinning and seeded with 22 million hiPSC-CMs. The in vitro assessment showed synchronized contractility of the hiPSC-CMs along the aligned fibers. 
3. An in vivo transplantation of the cardiac patch into a preclinical, large animal (porcine) MI model at one week after MI induction, that showed successful engraftment and survival of the hiPSC-CMs up to four weeks after transplantation.  
4. Establishing safety due to the absence of arrhythmias or teratoma formation, demonstrating a promising therapeutic approach for myocardial regeneration post-MI. Future studies in a larger control group and longer duration will determine efficacy and translation to stem cell therapy for patients with advanced heart failure. 

The team includes: Divya Sridharan, PhD, research scientist; Muhamad Mergaye, MS, lab manager; Syed Alvi, PhD, postdoctoral researcher; Syed Ashraf, former student assistant; and Helena Islam, MS, postdoctoral scholar, all in the Department of Emergency Medicine. Konstantinos Dean Boudoulas, MD, clinical professor of Internal Medicine; Yuchi Han, MD, professor of Internal Medicine; and Salman Pervaiz, research senior technician in the Department of Internal Medicine. Nikita Nair, student assistant in the Department of Radiology; Orlando Simonetti, PhD, professor of Radiology; and Juliet Varghese, PhD, assistant professor of Radiology. Matthew Joseph, senior research associate in the Davis Heart and Lung Research Institute; Heather Powell and Britani Blackstone in The Ohio State University College of Engineering; and Robert Hamlin, DVM, PhD, in the Ohio State College of Veterinary Medicine.