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Figure 2: Infarction represents a loss of myocytes at the cellular level where each functional myocyte represents a discrete pumping unit, and loss of myocytes on a large scale results in depression of global cardiac function, ultimately leading to heart failure and poor long-term prognosis. Three mechanisms of stem cellmediated repair have been proposed. 1) Transdifferentiation: GFP-labeled c-kit+/lin- stem cells (circled in green) transplanted into wild-type animals after MI have demonstrated formation of new myocytes positive for GFP expression. These cells initially synthesize unorganized a-actin (red cytoplasm), and upon differentiation, lose surface expression of c-kit, and organized sarcomeres (red lines) are visible histologically. 2) Fusion: LAC-Z+ stem cells (circled in cyan) transplanted into GFP transgenic animals have demonstrated myocytes coexpressing LAC-Z and GFP. 3) Paracrine Support: Secretion of VEGF (yellow) and other cytokines from transplanted stem cells have been shown to trigger formation of new blood vessels which results in improvement of post-MI cardiac function through paracrine mechanisms. |