title: Adult cardiac progenitor cell aggregates exhibit survival benefit both in vitro and in vivo.
abstract: BACKGROUND
  A major hurdle in the use of exogenous stems cells for therapeutic regeneration of injured myocardium remains the poor survival of implanted cells. To date, the delivery of stem cells into myocardium has largely focused on implantation of cell suspensions.
  
  
  RESULTS
  We hypothesize that delivering progenitor cells in an aggregate form would serve to mimic the endogenous state with proper cell-cell contact, and may aid the survival of implanted cells. Microwell methodologies allow for the culture of homogenous 3D cell aggregates, thereby allowing cell-cell contact. In this study, we find that the culture of cardiac progenitor cells in a 3D cell aggregate augments cell survival and protects against cellular toxins and stressors, including hydrogen peroxide and anoxia/reoxygenation induced cell death. Moreover, using a murine model of cardiac ischemia-reperfusion injury, we find that delivery of cardiac progenitor cells in the form of 3D aggregates improved in vivo survival of implanted cells.
  
  
  CONCLUSIONS
  Collectively, our data support the notion that growth in 3D cellular systems and maintenance of cell-cell contact improves exogenous cell survival following delivery into myocardium. These approaches may serve as a strategy to improve cardiovascular cell-based therapies.
authors.affiliation: Division of Cardiology and Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
authors.forename: Lifeng
authors.initials: L
authors.lastname: Kang
authors.forename: Yiling
authors.initials: Y
authors.lastname: Qiu
authors.forename: Jinhui
authors.initials: J
authors.lastname: Wu
authors.forename: Michelle
authors.initials: M
authors.lastname: Peng
authors.forename: Howard H
authors.initials: HH
authors.lastname: Chen
authors.forename: Gulden
authors.initials: G
authors.lastname: Camci-Unal
authors.forename: Ahmad F
authors.initials: AF
authors.lastname: Bayomy
authors.forename: David E
authors.initials: DE
authors.lastname: Sosnovik
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
authors.forename: Ronglih
authors.initials: R
authors.lastname: Liao
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002449:Cell Aggregation; D018929:Cell Culture Techniques; D015687:Cell Hypoxia; D002470:Cell Survival; D005260:Female; D006335:Heart Injuries / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009206:Myocardium / Q000166:cytology* / Q000473:pathology; D018384:Oxidative Stress; D058985:Side-Population Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology