Table 1 Mechanisms of the paracrine effect
Paracrine effect | Mechanisms |
|---|---|
Increased angiogenesis | Stem cells produce local signaling molecules that may improve perfusion and enhance angiogenesis to chronically ischemic tissue. Although the particular growth factors contributing to this neovascular effect remain to be defined, the list includes vascular endothelial growth factor, hepatocyte growth factor, and basic fibroblast growth factor 2 [84, 85]. |
Decreased inflammation | Stem cells appear to attenuate infarct size and injury by modulating local inflammation. When transplanted into injured tissue, the stem cell faces a hostile, nutrient-deficient, inflammatory environment and may release substances that limit local inflammation in order to enhance its survival. Recent studies implicate the release of the anti-inflammatory cytokine interleukin-10 as playing an integral role in modulating the activity of innate and adaptive immune cells, such as dendritic cells, T cells, and B cells [3, 83, 86]. |
Anti-apoptotic and chemotactic signaling | Stem cells in a third pathway promote salvage of tenuous or malfunctioning cell types at the infarct border zone. Injection of mesenchymal stem cells (MSCs) into a cryo-induced infarct reduces myocardial scar width 10 weeks later. MSCs appear to activate an anti-apoptosis signaling system at the infarct border zone and this effectively protects ischemia-threatened cell types from apoptosis [3, 39, 83]. |
Beneficial remodeling of the extracellular matrix | Stem cell transplantation alters the extracellular matrix, resulting in a more favorable post-infarct remodeling, strengthening of the infarct scar, and prevention of deterioration in organ function [3, 83, 87]. |
Activation of neighboring resident stem cells | Exogenous stem cell transplantation may activate neighboring resident tissue stem cells. These resident stem cells may possess growth factor receptors that can be activated to induce their migration and proliferation and promote both the restoration of dead tissue and the improved function in damaged tissue [3, 26]. |