title: Cardiac Stem Cell Hybrids Enhance Myocardial Repair.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  Two distinct and clonally derived CCs, CC1 and CC2, were used for this study. CCs improved left ventricular anterior wall thickness at 4 weeks post injury, but only CC1 treatment preserved anterior wall thickness 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 on combinatorial cell approaches to support myocardial regeneration.
authors.affiliation: From the Integrated Regenerative Research Institute, Department of Biology, San Diego State University, CA (P.Q., H.T.S., J.D.C., F.G.E.-S., M.M., K.M.B., J.M.E., A.D.L.T., L.O., R.A., N.A.G., M.A.S.); and Department of Pharmacology, University of California at Davis (N.H.).
authors.forename: Pearl
authors.initials: P
authors.lastname: Quijada
authors.affiliation: From the Integrated Regenerative Research Institute, Department of Biology, San Diego State University, CA (P.Q., H.T.S., J.D.C., F.G.E.-S., M.M., K.M.B., J.M.E., A.D.L.T., L.O., R.A., N.A.G., M.A.S.); and Department of Pharmacology, University of California at Davis (N.H.).
authors.forename: Hazel T
authors.initials: HT
authors.lastname: Salunga
authors.affiliation: From the Integrated Regenerative Research Institute, Department of Biology, San Diego State University, CA (P.Q., H.T.S., J.D.C., F.G.E.-S., M.M., K.M.B., J.M.E., A.D.L.T., L.O., R.A., N.A.G., M.A.S.); and Department of Pharmacology, University of California at Davis (N.H.).
authors.forename: Nirmala
authors.initials: N
authors.lastname: Hariharan
authors.affiliation: From the Integrated Regenerative Research Institute, Department of Biology, San Diego State University, CA (P.Q., H.T.S., J.D.C., F.G.E.-S., M.M., K.M.B., J.M.E., A.D.L.T., L.O., R.A., N.A.G., M.A.S.); and Department of Pharmacology, University of California at Davis (N.H.).
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Cubillo
authors.affiliation: From the Integrated Regenerative Research Institute, Department of Biology, San Diego State University, CA (P.Q., H.T.S., J.D.C., F.G.E.-S., M.M., K.M.B., J.M.E., A.D.L.T., L.O., R.A., N.A.G., M.A.S.); and Department of Pharmacology, University of California at Davis (N.H.).
authors.forename: Farid G
authors.initials: FG
authors.lastname: El-Sayed
authors.affiliation: From the Integrated Regenerative Research Institute, Department of Biology, San Diego State University, CA (P.Q., H.T.S., J.D.C., F.G.E.-S., M.M., K.M.B., J.M.E., A.D.L.T., L.O., R.A., N.A.G., M.A.S.); and Department of Pharmacology, University of California at Davis (N.H.).
authors.forename: Maryam
authors.initials: M
authors.lastname: Moshref
authors.affiliation: From the Integrated Regenerative Research Institute, Department of Biology, San Diego State University, CA (P.Q., H.T.S., J.D.C., F.G.E.-S., M.M., K.M.B., J.M.E., A.D.L.T., L.O., R.A., N.A.G., M.A.S.); and Department of Pharmacology, University of California at Davis (N.H.).
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Bala
authors.affiliation: From the Integrated Regenerative Research Institute, Department of Biology, San Diego State University, CA (P.Q., H.T.S., J.D.C., F.G.E.-S., M.M., K.M.B., J.M.E., A.D.L.T., L.O., R.A., N.A.G., M.A.S.); and Department of Pharmacology, University of California at Davis (N.H.).
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Emathinger
authors.affiliation: From the Integrated Regenerative Research Institute, Department of Biology, San Diego State University, CA (P.Q., H.T.S., J.D.C., F.G.E.-S., M.M., K.M.B., J.M.E., A.D.L.T., L.O., R.A., N.A.G., M.A.S.); and Department of Pharmacology, University of California at Davis (N.H.).
authors.forename: Andrea
authors.initials: A
authors.lastname: De La Torre
authors.affiliation: From the Integrated Regenerative Research Institute, Department of Biology, San Diego State University, CA (P.Q., H.T.S., J.D.C., F.G.E.-S., M.M., K.M.B., J.M.E., A.D.L.T., L.O., R.A., N.A.G., M.A.S.); and Department of Pharmacology, University of California at Davis (N.H.).
authors.forename: Lucia
authors.initials: L
authors.lastname: Ormachea
authors.affiliation: From the Integrated Regenerative Research Institute, Department of Biology, San Diego State University, CA (P.Q., H.T.S., J.D.C., F.G.E.-S., M.M., K.M.B., J.M.E., A.D.L.T., L.O., R.A., N.A.G., M.A.S.); and Department of Pharmacology, University of California at Davis (N.H.).
authors.forename: Roberto
authors.initials: R
authors.lastname: Alvarez
authors.affiliation: From the Integrated Regenerative Research Institute, Department of Biology, San Diego State University, CA (P.Q., H.T.S., J.D.C., F.G.E.-S., M.M., K.M.B., J.M.E., A.D.L.T., L.O., R.A., N.A.G., M.A.S.); and Department of Pharmacology, University of California at Davis (N.H.).
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Gude
authors.affiliation: From the Integrated Regenerative Research Institute, Department of Biology, San Diego State University, CA (P.Q., H.T.S., J.D.C., F.G.E.-S., M.M., K.M.B., J.M.E., A.D.L.T., L.O., R.A., N.A.G., M.A.S.); and Department of Pharmacology, University of California at Davis (N.H.). heartman4ever@icloud.com.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sussman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D056988:Anterior Wall Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D048429:Cell Size; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D010641:Phenotype; D051381:Rats; D020127:Recovery of Function; D012038:Regeneration; D013318:Stroke Volume; D013997:Time Factors; D014162:Transfection; D018183:Transplantation Chimera; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers
keywords: cell fusion; mesenchymal stromal cells; myocardial infarction; myocytes, cardiac; stem cells