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

• Published in: Circulation research 2016-08, Vol.119 (5), p.635-651
• Main 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
• Format: Article
• Language: English
• Subjects: Animals; Cell Survival - physiology; Cell- and Tissue-Based Therapy - methods; Cell- and Tissue-Based Therapy - trends; Female; Male; Myocardial Infarction - pathology; Myocardial Infarction - therapy; Myocytes, Cardiac - physiology; Rats; Rats, Inbred F344; Stem Cell Transplantation - methods; Stem Cell Transplantation - trends; Stem Cells - physiology; Ventricular Function, Left - physiology
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/CIRCRESAHA.116.308937

RATIONALE:The effects of c-kit 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