Circulation Research

RES

Cardiac Stem Cell Hybrids Enhance Myocardial Repair

CardioChimeras Enhance Myocardial Repair

CIRCRES/2015/306838

10.1161/CIRCRESAHA.115.306838 117

09/28/15

Bridges-Lyman Gemma

410-3275005

410-3279322

Hajjar, Roger Icahn School of Medicine at Mount Sinai

Prof.

Mark

Sussman

heartman4ever@icloud.com

Prof.

San Diego State University

5500 Campanile Drive North

Life Sciences 426

San Diego

California

92182

UNITED STATES

United Sta-619-594-2983

United Sta-619-594-2610

11355

Pearl

Quijada

San Diego State University

pearlquijada@gmail.com

258043

Hazel

Salunga

San Diego State University

hazelsalunga2@gmail.com

274801

Nirmala

Hariharan

San Diego State University

nirmala.hariharan@gmail.com

154398

Jonathan

Cubillo

San Diego State University

jon.d.cubillo@gmail.com

274753

Farid

El-Sayed

San Diego State University

fgehwf@mail.missouri.edu

274754

Maryam

Moshref

San Diego State University

mary.moshref@gmail.com

274755

Kristin

Marie

Bala

San Diego State University

kristin.bala@yahoo.com

274756

Jacqueline

Maria

Emathinger

San Diego State University

jmemathinger@gmail.com

190643

Andrea

De La Torre

San Diego State University

andreadelatorre615@gmail.com

103423

Lucia

Ormachea

San Diego State University

lucituch@gmail.com

103014

Roberto

Alvarez

San Diego State University

ralvarez@mail.sdsu.edu

269402

Natalie

Gude

San Diego State University

ngude@mail.sdsu.edu

103022

Mark

Sussman

San Diego State University

heartman4ever@icloud.com

11355

05/12/2015

07/21/2015

07/29/2015

07/30/2015

Regular Article

cell fusion

Rationale: Dual cell transplantation of cardiac progenitor cells (CPCs) and mesenchymal stem cells (MSCs) after infarction improves myocardial repair and performance in large animal models relative to delivery of either cell population. Objective:To demonstrate that CardioChimeras (CCs) formed by fusion between CPCs and MSCs have enhanced reparative potential in a mouse model of myocardial infarction relative to individual stem cells or combined cell delivery. Methods and Results: Two distinct and clonally derived CCs, CC1 and CC2 were utilized for this study. CCs improved left ventricular anterior wall thickness (AWT) at 4 weeks post injury, but only CC1 treatment preserved AWT at 18 weeks. Ejection fraction was enhanced at 6 weeks in CCs, and functional improvements were maintained in CCs and CPC + MSC groups at 18 weeks. Infarct size was decreased in CCs, whereas CPC + MSC and CPC parent groups remained unchanged at 12 weeks. CCs exhibited increased persistence, engraftment, and expression of early commitment markers within the border zone relative to combinatorial and individual cell population-injected groups. CCs increased capillary density and preserved cardiomyocyte size in the infarcted regions suggesting CCs role in protective paracrine secretion. Conclusions: CCs merge the application of distinct cells into a single entity for cellular therapeutic intervention in the progression of heart failure. CCs are a novel cell therapy that improves upon combinatorial cell approaches to support myocardial regeneration.

yes

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CircRes_CIRCRES-2015-306838_Quijada_258043_disclosure.pdf

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CircRes_CIRCRES-2015-306838_Salunga_274801_disclosure.pdf

CircRes_CIRCRES-2015-306838_Salunga_274801_copyright.pdf

PAP: 07/30/15 Funding: Howard Hughes Medical Institute (HHMI): No National Institutes of Health (NIH): Yes Not applicable for this manuscript: No Other: Yes Wellcome Trust: No Subject Codes: [137] Cell biology/structural biology [147] Growth factors/cytokines [115] Remodeling [4] Acute myocardial infarction [105] Contractile function gbridgeslyman