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Importance of cell-cell contact in the therapeutic benefits of cardiosphere-derived cells.

ABSTRACT: Cardiosphere-derived cells (CDCs) effect therapeutic regeneration after myocardial infarction (MI) both in animal models and in humans. Here, we test the hypothesis that cell-cell contact plays a role in mediating the observed therapeutic benefits of CDCs, above and beyond conventional paracrine effects. Human CDCs or vehicle were injected into immunodeficient (SCID) mouse hearts during acute MI. CDC transplantation augmented the proportion of cycling (Ki67(+) ) cardiomyocytes and improved ventricular function. CDC-conditioned media only modestly augmented the percentage of Ki67(+) cardiomyocytes (>control but

SUBMITTER: Xie Y

PROVIDER: S-EPMC4138271 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Importance of cell-cell contact in the therapeutic benefits of cardiosphere-derived cells.

Xie Yucai Y Ibrahim Ahmed A Cheng Ke K Wu Zhijun Z Liang Wenbin W Malliaras Konstantinos K Sun Baiming B Liu Weixin W Shen Deliang D Cheol Cho Hee H Li Taosheng T Lu Lin L Lu Guoping G Marbán Eduardo E

Stem cells (Dayton, Ohio) 20140901 9

Cardiosphere-derived cells (CDCs) effect therapeutic regeneration after myocardial infarction (MI) both in animal models and in humans. Here, we test the hypothesis that cell-cell contact plays a role in mediating the observed therapeutic benefits of CDCs, above and beyond conventional paracrine effects. Human CDCs or vehicle were injected into immunodeficient (SCID) mouse hearts during acute MI. CDC transplantation augmented the proportion of cycling (Ki67(+) ) cardiomyocytes and improved ventr ...[more]

PMID: 24802280

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Project description:OBJECTIVES:This study sought to report full 1-year results, detailed magnetic resonance imaging analysis, and determinants of efficacy in the prospective, randomized, controlled CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial. BACKGROUND:Cardiosphere-derived cells (CDCs) exerted regenerative effects at 6 months in the CADUCEUS trial. Complete results at the final 1-year endpoint are unknown. METHODS:Autologous CDCs (12.5 to 25 × 10(6)) grown from endomyocardial biopsy specimens were infused via the intracoronary route in 17 patients with left ventricular dysfunction 1.5 to 3 months after myocardial infarction (MI) (plus 1 infused off-protocol 14 months post-MI). Eight patients were followed as routine-care control patients. RESULTS:In 13.4 months of follow-up, safety endpoints were equivalent between groups. At 1 year, magnetic resonance imaging revealed that CDC-treated patients had smaller scar size compared with control patients. Scar mass decreased and viable mass increased in CDC-treated patients but not in control patients. The single patient infused 14 months post-MI responded similarly. CDC therapy led to improved regional function of infarcted segments compared with control patients. Scar shrinkage correlated with an increase in viability and with improvement in regional function. Scar reduction correlated with baseline scar size but not with a history of temporally remote MI or time from MI to infusion. The changes in left ventricular ejection fraction in CDC-treated subjects were consistent with the natural relationship between scar size and ejection fraction post-MI. CONCLUSIONS:Intracoronary administration of autologous CDCs did not raise significant safety concerns. Preliminary indications of bioactivity include decreased scar size, increased viable myocardium, and improved regional function of infarcted myocardium at 1 year post-treatment. These results, which are consistent with therapeutic regeneration, merit further investigation in future trials. (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction [CADUCEUS]; NCT00893360).

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Importance of cell-cell contact in the therapeutic benefits of cardiosphere-derived cells.

Publications

Importance of cell-cell contact in the therapeutic benefits of cardiosphere-derived cells.

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