Repeated Administrations of Cardiac Progenitor Cells Are Markedly More Effective Than a Single Administration: A New Paradigm in Cell Therapy. Issue 5 (19th August 2016)

• Record Type: Journal Article
• Authors: Tokita, Yukichi; Tang, Xian-Liang; Li, Qianhong; Wysoczynski, Marcin; Hong, Kyung U.; Nakamura, Shunichi; Wu, Wen-Jian; Xie, Wei; Li, Ding; Hunt, Greg; Ou, Qinghui; Stowers, Heather; Bolli, Roberto
• Is Part Of: Circulation research. Volume 119:Issue 5(2016)
• Publication Date: 2016-08-19
• Subjects: cardiac progenitor cells -- cell therapy -- collagen -- left ventricular function -- myocardial infarction -- reperfusion injury -- ventricular remodeling; Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.116.308937
• Languages: English
• ISSNs: 0009-7330

Abstract

Abstract : Rationale: : The effects of c-kit POS 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 3 CPC infusions have greater efficacy than 1 infusion. Methods and Results: : Rats with a 30-day-old myocardial infarction received 1 or 3 CPC infusions into the LV cavity, 35 days apart. Compared with vehicle-treated rats, the single-dose group exhibited improved LV function after the first infusion (consisting of CPCs) but not after the second and third (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 versus 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 evaluate the effectiveness of a cell product properly. In addition, we describe a new method that enables studies of repeated cell administrations in rodents. Abstract : Supplemental Digital Content is available in the text.