Repeated Administrations of Cardiac Progenitor Cells Are Markedly More Effective Than a Single Administration: A New Paradigm in Cell Therapy
Published Date:Jun 30 2016
Source:Circ Res. 119(5):635-651.
Pubmed Central ID:PMC4992406
Funding:H75 DP424252/DP/NCCDPHP CDC HHS/United States
P01 HL078825/HL/NHLBI NIH HHS/United States
R01 HL055757/HL/NHLBI NIH HHS/United States
R01 HL068088/HL/NHLBI NIH HHS/United States
R01 HL074351/HL/NHLBI NIH HHS/United States
The effects of c-kitPOS cardiac progenitor cells (CPCs) (and adult cell therapy in general) on left ventricular (LV) function have been regarded as modest or inconsistent.
To determine whether three CPC infusions have greater efficacy than one infusion.
Methods and Results
Rats with a 30-day-old myocardial infarction received one or three CPC infusions into the LV cavity, 35 days apart. Compared with vehicle-treated rats, the single-dose group exhibited improved LV function after the 1st infusion (consisting of CPCs) but not after the 2nd and 3rd (vehicle). In contrast, in the multiple-dose group regional and global LV function improved by a similar degree after each CPC infusion, resulting in greater cumulative effects. For example, the total increase in LV ejection fraction was approximately triple in the multiple-dose group vs. the single-dose group (P<0.01). The multiple-dose group also exhibited more viable tissue and less scar, less collagen in the risk and noninfarcted regions, and greater myocyte density in the risk region.
This is the first demonstration that repeated CPC administrations are markedly more effective than a single administration. The concept that the full effects of CPCs require repeated doses has significant implications for both preclinical and clinical studies; it suggests that the benefits of cell therapy may be underestimated or even overlooked if they are measured after a single dose, and that repeated administrations are necessary to properly evaluate the effectiveness of a cell product. In addition, we describe a new method that enables studies of repeated cell administrations in rodents.
Supporting Files:No Additional Files
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