| Description |
Chronic heart failure (CHF) is a life-altering long-term condition that contributes a substantial burden to our healthcare system. It is caused by a maladaptive remodeling of the heart mediated through fibroblast synthesis, degradation, and modification of extracellular matrix (ECM). It is currently managed through pharmacologic intervention or medical device treatment, but can be reversed only through heart transplantation. Cell therapy is a new approach to treating CHF that promises to prevent and potentially reverse cardiac remodeling through interaction with cardiac fibroblasts. Adherent bone marrow derived stem cells (MSC) are one of the most promising candidates for use in cell therapies. The major challenge hindering standard clinical application of MSC therapy is limited understanding of how MSC interact with heart cells to reverse remodeling. Numerous techniques are available to harvest, isolate, and modify MSC, however these techniques are believed to influence the efficacy of the treatment. Current techniques for evaluating efficacy of MSC treatments are either prohibitively difficult or significantly limited in their ability to assess functional changes. Establishing an in vitro platform for evaluating the influence of MSC coculture on performance characteristics of cardiac fibroblasts is a logical and efficient step prior to successful clinical implementation of MSC therapy. The objective of this research was to develop a threedimensional (3D) tissue model that allows investigation of the underlying mechanism responsible for MSC mediated cardiac regeneration. The three phases of this work included: (1) development of a biomaterial substrate capable of sustaining fibroblast attachment, proliferation, and alignment, (2) development of a culture platform and seeding techniques capable of providing sufficient mass transport to sustain a relatively thick 3D scaffold populated with both fibroblasts and MSC (3) application of the substrate and culture platform to evaluate changes in mechanical properties and cell distribution resulting from MSC coculture with cardiac fibroblasts. |
