Targeting cellular therapeutics in a pre-clinical model of myocardial infarction

Sriram Neelamegham Lab

fluorescent image showing slex on the stem cell surface

Identifying new technologies to improve stem cell therapy for an array of cardiovascular diseases. 

Overview

The blockage of the arteries that feed blood to the heart results in heart attacks, also known as myocardial infarction. This injury causes heart tissue death, and it negatively impacts patient survival and long-term quality of life. Stem cell therapy is a promising approach to restore heart function since these cells promote tissue repair and may reduce heart muscle damage. The major challenge here lies in the targeting of the stem cell therapy specifically to the compromised area of the heart that can benefit from regenerative medicine. This is complex since the infarcted region itself is poorly perfused, and direct stem cell injection into this region would simply result in cell death. Thus, we need to target the large compromised region surrounding the infarct. In this project, supported by the American Heart Association, the Neelamegham laboratory works on glycoengineering stem cells with a unique carbohydrate recognition motif called ‘sialyl Lewis-X’ in the context of specific glycoproteins. Decorating the stem cells with this sugar structure enhances the homing of mesenchymal and cardiosphere-derived stem cells to the blood vessels of the injured heart, which express adhesion molecules called ‘selectins’ at their sites of inflammation. Testing cell homing in large animal swine models are part of this project, and these are conducted in collaboration with Prof. John M. Canty Jr., Chief of the Division of Cardiovascular Medicine, School of Medicine and Biomedical Sciences. Successful completion of this work will result in new technologies to improved stem cell therapy for an array of cardiovascular diseases.

Resulting Publications

  • Momeni A, Neelamegham S, Parashurama N. ‘Current challenges for the targeted delivery and molecular imaging of stem cells in animal models’ Bioengineered. 2016 Nov 4:1-9.
  • Lo CY, Weil BR, Palka BA, Momeni A, Canty JM Jr, Neelamegham S. ‘Cell surface glycoengineering improves selectin-mediated adhesion of mesenchymal stem cells (MSCs) and cardiosphere-derived cells (CDCs): Pilot validation in porcine ischemia-reperfusion model.’ Biomaterials. 2016; 74:19-30
  • Lo CY, Antonopoulos A, Dell A, Haslam SM, Lee T, Neelamegham S. ‘The use of surface immobilization of P-selectin glycoprotein ligand-1 on mesenchymal stem cells to facilitate selectin mediated cell tethering and rolling.’ Biomaterials. 2013 ;34(33):8213-22.

Students on this Project

  • Arezoo Momeni, BS