Repeated Administrations of Cardiac Progenitor Cells Are Markedly More Effective Than a Single Administration: A New Paradigm in Cell Therapy

Details

• Alternative Title:
  Circ Res
• Personal Author:
  Tokita, Yukichi ; Tang, Xian-Liang ; Li, Qianhong ; Wysoczynski, Marcin ; Hong, Kyung U ; Bolli, Roberto A. ; Nakamura, Shunichi ; Wu, Wen-Jian ; Xie, Wei ; Li, Ding ; Hunt, Greg ; Ou, Qinghui ; Stowers, Heather ; Bolli, Roberto
  More +
• Description:
  Rationale ; 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. ; Objective ; 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. ; Conclusions ; 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.
• Subjects:
  • Article
  • Cell therapy
  • cardiac progenitor cells
  • myocardial infarction
  • ischemia reperfusion injury
  • left ventricular function
  • left ventricular remodeling
  • Animals
  • Cell Survival
  • Cell- and Tissue-Based Therapy
  More +
• Source:
  Circ Res. 119(5):635-651.
• Pubmed ID:
  27364016
• Pubmed Central ID:
  PMC4992406
• Document Type:
  Journal Article
• Funding:
  R01 HL055757/HL/NHLBI NIH HHS/United States ; H75 DP424252/DP/NCCDPHP CDC HHS/United States ; P01 HL078825/HL/NHLBI NIH HHS/United States ; R01 HL074351/HL/NHLBI NIH HHS/United States ; UM1 HL113530/HL/NHLBI NIH HHS/United States ; R01 HL068088/HL/NHLBI NIH HHS/United States
• Volume:
  119
• Issue:
  5
• Download URL:
  https://stacks.cdc.gov/view/cdc/41002/cdc_41002_DS1.pdf
• File Type:
  [PDF - 4.95 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:ad4e4debe16e0f9854b46d22590d9ba5c50fd10f5f4cc612222fc111fa565b62