Cell-derived Extracellular Matrix in Lymphangiogenesis and Cardiac Patch Engineering
Abstract
The importance of tissue-specific microenvironments in achieving physiological cell and tissue functions has spurred the advancement of extracellular matrix (ECM) scaffolds for tissue engineering. Unlike defined scaffolds containing a few natural or synthetic components, ECM-based scaffolds closely mimic the composition of the complex native microenvironment to provide key biochemical cues that regulate the fate, viability, and function of transplanted cells. Although tissue/organ-derived ECM is commonly used, it is associated with problems including autologous tissue scarcity, risk of pathogen transfer, and immune rejection when allogenic and xenogenic tissues are used. Therefore, human cell-derived ECM holds great potential because of their pathogen screening and patient-specific design abilities.
The objectives of this study are to investigate the roles of specific cell-derived ECM scaffolds to enhance stem cell-stimulated lymphangiogenesis and to provide a cardiac specific microenvironment. In the first aim, a human mesenchymal stem (hMSC) sheet, containing cells and cell-secreted ECM, was developed to stimulate lymphangiogenesis for treating lymphedema. It was found that the ECM played a role as a bioactive cell delivery vehicle that not only delivered cells but stored growth factors to activate lymphangiogenesis. The injection of MSC sheet fragments augmented the therapeutic effect of MSCs by stimulating lymphatic vessel regeneration and wound closure in a mouse tail lymphedema model. In the second aim, a completely biological and anisotropic cardiac ECM scaffold was produced from pluripotent stem cell-derived cardiac fibroblast (PSC-CF) sheet to engineer a cardiac patch. This study demonstrated that PSC-CF-derived cardiac scaffold carries cardiac-specific biochemical and structural cues that are essential for the maturation of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). The scaffold showed comparable levels of structural proteins and matrix-bound growth factors as primary CF derived scaffold and promoted structural and functional maturation of iPSC-CMs.
Overall, this work emphasizes the significance of cell-derived ECM in providing biochemical and structural basics for tissue engineering. It can be used as a delivery vehicle for tissue regeneration such as for MSC therapy in treating lymphedema and for engineering a completely biological tissues for cardiac repair.
Subject
Cell-derived extracellular matrixmesenchymal stem cell
induced pluripotent stem cell
lymphangiogenesis
cardiac patch
Citation
Jia, Wenkai (2021). Cell-derived Extracellular Matrix in Lymphangiogenesis and Cardiac Patch Engineering. Doctoral dissertation, Texas A&M University. Available electronically from https : / /hdl .handle .net /1969 .1 /195348.