Results of cellular therapy for ischemic myocardial dysfunction. A review

Ischemic heart disease (IHD) terminally injures the heart with attendant myocardial dysfunction. Effective therapy for IHD is limited when the myocardium cannot be revascularized. Thus, alternative therapies for IHD are emerging, including immature cell transplantation to injured hearts. One experience with this technique and its effect upon indices of myocardial performance are reviewed.

Micromanometry and sonomicrometry determined in vivo left ventricular pressure (P) and segment length (SL) following irreversible myocardial injury and 3 weeks after cell transplantation with either autologous skeletal myoblasts or autologous dermal fibroblasts. Systolic performance was based on the linear regression of stroke work and end-diastolic (ED) SL. Diastolic properties were assessed using the curvilinear relationships between LVEDP and strain (e). Cellular engraftment was assessed histologically at study conclusion.

Skeletal myoblasts formed dense, engrafted tissue within injured hearts but did not extend beyond the borders of the injury. Engrafted fibroblasts were more uniformly distributed throughout the injured region. Diastolic performance improved following cell transplantation with either myoblasts or fibroblasts. Cell transplantation with skeletal myoblasts also improved contractile performance, but fibroblast transfer was associated with a significant decrement in systolic performance.

Cellular transplantation with either myoblasts or fibroblasts can successfully and reliably regenerate viable tissue within areas of terminally injured heart. Cellular engraftment favorably alters the regional geometry within the injured heart, conferring improved functional indices upon treated animals. Further investigation is needed to ensure the safety of these techniques, to ascertain the optimal cell type and delivery method for transplantation, and to improve the reproducibility of cellular engraftment.