SC BioCRAFT

Project VII

Ying Mei

Combinatorial Development of Biomaterials for Cardiac Tissue Regeneration

Target Investigator
Dr. Ying Mei
Assistant Professor of Bioengineering
Clemson University

Cardiovascular disease, the leading cause of death and disability worldwide, claims more lives than all kinds of cancers combined. Ischaemic heart disease (IHD) and myocardial infarction (MI) are major contributors to cardiovascular morbidity and mortality; they usually are associated with irreversible death of cardiomyocyte and lead to permanent loss of heart function. Human embryonic stem cell (hESC) and human induced pluripotent stem cell (hIPSC) technologies hold remarkable promise for myocardial regeneration because of their unquestionable capacity to produce de novo cardiomyocytes.

Two key limitations of existing hESC and hIPSC technology are:

  1. the lack of chemically defined, completely synthetic substrates to derive clinicalgrade cardiac cells, and
  2. the suboptimal efficiency associated with stem-cell differentiation into cardiac cells.

 

Synthetic short peptides derived from extracellular matrix (ECM) proteins and growth factors have been extensively used to enhance cell adhesion and proliferation on synthetic materials. However, their low affinity for cell-surface receptors limits their ability to direct stem-cell differentiation. Using my expertise in peptide synthesis, polymer science, combinatorial approach, and hESC and hIPSC technology, I propose to develop completely synthetic, biologically functional substrates to direct hESCs and hIPSCs to differentiate into clinical-grade cardiomyocytes in a xeno-free, chemically defined condition.

The central hypothesis of this project is that the substrates with a variety of high density peptides derived from multiple cardiogenic ECM proteins and growth factors that are essential to cardiogenesis can effectively induce cardiac differentiation of hESCs and hIPSCs through high affinity, synergic engagements between peptides and cell-surface receptors.

Accordingly, our Specific Aims are:

  1. Develop completely synthetic, biologically functional culture substrates using combinatorial peptide-polymer arrays for directed cardiac differentiation; and
  2. Develop a rapid, efficient method to differentiate hESCs and hIPSCs into homogeneous populations of functional cardiomyocytes in xeno-free, chemically defined conditions.