The Alchemist's Nightmare: Might Mesenchymal Stem Cells That Are Recruited to Repair the Injured Heart Be Transformed Into Fibroblasts Rather Than Cardiomyocytes?

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The injection of mesenchymal stem cells into the injured myocardium to induce cardiac regeneration has yielded disappointing results, conceivably because cells with cardioreparative potential must be supplied for long periods of time to produce a salutary effect. Accordingly, investigators have devised ways of directing such cells to the heart on an ongoing basis: by enhancing the action of endogenous peptides that function as cardiac homing signals (eg, stromal cell-derived factor-1). Stromal cell-derived factor-1 is released during acute cardiac injury and heart failure, but it has a short half-life because of degradation by dipeptidyl peptidase-4. Inhibition of dipeptidyl peptidase-4 potentiates the actions of stromal cell-derived factor-1 and, theoretically, could enhance cardiac recovery. However, in large-scale trials in patients with type 2 diabetes mellitus, dipeptidyl peptidase-4 inhibitors have not reduced the risk of atherosclerotic ischemic events, and they have unexpectedly increased the risk of heart failure, most probably heart failure with a preserved ejection fraction. Such an outcome might be explained if the channeling of mesenchymal stem cells to the heart by the actions of stromal cell-derived factor-1 (especially from nearby adipose tissue) were followed by the transformation of these cells into fibroblasts rather than cardiomyocytes. This concern has been

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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