Comparison of benefits on myocardial performance of cellular cardiomyoplasty with skeletal myoblasts and fibroblasts

Cellular cardiomyoplasty (CCM), or introduction of immature cells into term inally injured heart, can mediate repair of chronically injured myocardium. Several different cell types, ranging from embryonic stem cells to autolog ous skeletal myoblasts, have been successfully propagated within damaged he art and shown to improve myocardial performance, However, it is unclear if the functional advantages associated with CCM depend upon the use of myogen ic cells or if similar results can be seen with other cell types. Thus, we compared indices of regional contractile (systolic) and diastolic myocardia l performance following transplantation of either autologous skeletal myobl asts (Mb) or dermal fibroblasts (Fb) into chronically injured rabbit heart. In vivo left ventricular (LV) pressure (P) and regional segment length (SL ) were determined in 15 rabbits by micromanometry and sonomicrometry 1 week following LV cryoinjury (CRYO) and again 3 weeks after autologous skeletal Mb or dermal Fb transplantation. Quantification of systolic performance wa s based on the linear regression of regional stroke work and end-diastolic (ED) SL. Regional diastolic properties were assessed using the curvilinear relationships between LVEDP and strain (epsilon) as well as LVEDP and EDSL. At study termination, cellular engraftment was characterized histologicall y in a blinded fashion. Indices of diastolic performance were improved foll owing CCM with either Mb or Fb. However, only Mb transplantation improved s ystolic performance; Fb transfer actually resulted in a significant decline in systolic performance. These data suggest that both contractile and nonc ontractile cells can improve regional material properties or structural int egrity of terminally injured heart, as reflected by improvements in diastol ic performance. However, only Mb improved systolic performance in the damag ed region, supporting the role of myogenic cells in augmenting contraction. Further studies are needed to define the mechanism by which these effects occur and to evaluate the long-term safety and efficacy of CCM with any cel l type.