Editors' ChoiceMyocardial Infarction

Shaking up cellular therapy

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Science Translational Medicine  18 Apr 2018:
Vol. 10, Issue 437, eaat4475
DOI: 10.1126/scitranslmed.aat4475

Abstract

Stem cell preparation technique determines the outcome of transplant therapy for myocardial infarction.

The promise of mesenchymal stem cell (SC) therapy has excited many, in particular for treatment of injured myocardium. Cells can be injected intravenously, into coronary arteries, or directly into the myocardium, but typically only 10% survive in the injured myocardium environment after one week. Implanting SC sheets improves cell survival, revascularization, and angiogenesis, which are vital components for successful therapy. Yet insufficient nutrient supply remains the major hurdle in maintaining viable SC sheet function after transplant. The therapeutic effect of SC sheets cannot be evaluated unless some level of consistency is introduced in their preparation, but there is a lot of variation in culture strategies and conflicting opinions on appropriate cell seeding density.

Wang and colleagues have now discovered a method of preparing stem cell sheets for myocardial infarction (MI) therapy that appears to overcome these issues. Their study demonstrates that having an appropriate sheet scaffold with sufficient nutrient supply in vitro is imperative for successful in vivo outcomes. Immersion of decellularized porcine pericardium in aspartic acid solution and cross-linking vascular epithelial growth factors improved scaffold behavior as compared with the previously favored decellularized porcine pericardium alone. Wang and colleagues designed a dynamic system where a perfusion culture system connected to a peristaltic pump exposed multilayered SC sheets to mechanical loading to provide flowing nutrition. After 48 hours of dynamic culture conditions, the SC sheets demonstrated improved bioactivity as compared with SC sheets cultured in traditional static conditions. The researchers tested the in vivo response to dynamically prepared SC sheets in a rat MI model. Four weeks after MI, rats receiving dynamically prepared SC sheets had improved cardiac function and reduced infarct tissue area compared with rats that received SC sheets cultured under static conditions and controls. Imaging also revealed improved vascularization in the group receiving dynamically prepared SC sheets. Although further studies in larger animal models will be needed to optimize system parameters of Wang and colleagues’ model, these results illustrate the notable potential of SC therapy for MI with appropriate preparation.

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