Transplanted stem cells improve heart function after injury by triggering an immune response, reveals a mouse study published online in Nature this week.
Thousands of patients have already taken part in clinical trials of cardiac cell therapy in which adult stem cells are injected into damaged heart tissue, but the results have been mixed and often disappointing. The rationale comes from animal studies in which modest benefits have been demonstrated, but the processes that might underlie the positive effects of stem cells have been debated.
Jeffery Molkentin and colleagues now show that the beneficial effect in their model does not result from the stem cells differentiating to become new heart muscle cells, as suggested by previous work. Instead, the transplanted cells generate an acute immune response that involves large numbers of specific macrophages, which then alter the activity of local fibroblasts and enhance the mechanical properties of the injured tissue area. The same effects were achieved when the authors injected non-viable stem cells, or treated the animals with a chemical that induces the immune response. This finding suggests that it is the immune response, and not signals emanating from the stem cells themselves, that helps the heart to repair.
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