Grants and Contracts Details
To address the persistent shortage of patient-matched hearts, the biomedical research community has aggressively pursued the removal of cells from unmatched hearts (decell) and the repopulation of the remaining extracellular matrix with patient derived cells (recell). In these decell/recell strategies, accurate heart geometry is preserved, immunogenic materials are eliminated, and functional autologous cells are returned to the heart. Critically, there are no methods to precisely and accurately control the location of a given cell population during recell, making a full reconstruction of a functioning, natural heart impossible. To solve this problem, we will introduce create a novel recell process which uses binding motifs on the cell surface and on targeted locations in the heart scaffold to specifically load a cell type at its physiological location. Cell surfaces will be tagged with biotin, and we will pattern streptavidin onto a decell heart. The cells will be incubated and rinsed, yielding the primary cells in the targeted location. Additional cell types are loaded sequentially. Thus, we hypothesize that targeted cell adhesion will enable the intentional positioning of multiple cell populations with single-cell resolution in a decell heart. Aim 1 will establish the spatial resolution, specificity of adhesion, and cell lineage generality of our novel patterned heart recell procedure. Decell mouse hearts will be biotinylated through incubation in photobiotin and exposure to patterned blue light and incubation with streptavidin. Cells will be biotinylated and introduced to hearts. Metrics will be determined for heart-specific phenotypes and multiple methods for photopatterning, cell biotinylation, and sequential cell patterning. Aim 2 will examine the tissue function of patterned heart tissues. Cell viability for all phenotypes will be determined for up to one week post recell. Cardiomyocyte function will be evaluated with immunohistochemistry and conctractility assays. Endothelial cell function will be evaluated with immunohistochemistry and junction analysis. In this improved recell strategy, physiologically-accurate assembly of a non-immunogenic, functioning natural heart from autologous cells is enabled for the first time.
|Effective start/end date||7/1/18 → 6/30/21|
- American Heart Association: $153,666.00
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