Abstract 14862: Superiority of Human Pluripotent Stem Cell-Derived Cardiovascular Progenitors or Cardiomyocytes Over Bone Marrow Cells for Post-Infarction Ventricular Repair
Cell therapies to repair the failing heart could offer great clinical benefit but few studies directly comparing efficacy between cell types have been performed. Here we sought to compare the cardiac repair efficacy of three promising human cell types: bone marrow mononuclear cells (hBMMNC), human embryonic stem cell-derived cardiomyocytes (hESC-CM) and hESC-derived cardiovascular progenitors (hESC-CVP).
Methods/Results: Myocardial infarction (MI) was performed in athymic nude rats by 60 min ischemia then reperfusion. Baseline echocardiography was performed 4 days after MI before transplantation with 10x10^6 cells into the central infarct region and border zones. Rats were randomly assigned to the following groups: hESC-CVP n=10, hESC-CM n=11, hBMMNC n=11 and non-cardiac cells (control) derived from human ESCs (hNC) n=13. Flow cytometry revealed 77% of hESC-CVP cells were KDR+/PDGFRα+ whilst 69% of hES-CM cells were cardiac troponin-T+. At 4d after MI there was no significant difference in left ventricular function (LVF; by fractional shortening) between the groups (averaging 30%, p=0.31). At 32d there was deterioration in LVF in the hNC group whilst LVF was partially restored in hESC-CVP and hESC-CM groups (see fig). Interestingly, BMMNC treatment prevented deterioration but did not restore LVF. Human cells were identified by in situ hybridation with a human pan centromeric probe and graft composition analyzed by immunohistochemistry. At 32d after MI, substantial grafts of human cardiac muscle (expressing β-myosin heavy chain and NKX2.5) were consistently seen in hESC-CVP (11+/-8% of scar) and hESC-CM (20+/-4% of scar) groups. In contrast no (hBMMNC) or few (hNC) human cells were detected in other groups.
Conclusion: Both hESC-derived CVP and CM are capable of long-term engraftment in the infarcted rat heart where partial restoration in LVF is seen after cell injection. In contrast hBMMNC do not engraft but prevent LVF deterioration without restoration.
- © 2012 by American Heart Association, Inc.