title: Immunologic Network and Response to Intramyocardial CD34+ Stem Cell Therapy in Patients With Dilated Cardiomyopathy.
abstract: BACKGROUND
  Although stem cell therapy (SCT) is emerging as a potential treatment for patients with dilated cardiomyopathy (DCM), clinical response remains variable. Our objective was to determine whether baseline differences in circulating immunologic and nonimmunologic biomarkers may help to identify patients more likely to respond to intramyocardial injection of CD34(+)-based SCT.
  
  
  RESULTS
  We enrolled from January 3, 2011 to March 5, 2012 37 patients with longstanding DCM (left ventricular ejection fraction [LVEF] <40%, New York Heart Association functional class III) who underwent peripheral CD34(+) stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) and collection by means of apheresis. CD34(+) cells were labeled with (99m)Tc-hexamethylpropyleneamine oxime to allow assessment of stem cell retention at 18 hours. Response to SCT was predefined as an increase in LVEF of ≥5% at 3 months. The majority (84%) of patients were male with an overall mean LVEF of 27 ± 7% and a median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of 2,774 pg/mL. Nineteen patients (51%) were responders to SCT. There was no significant difference between responders and nonresponders regarding to age, sex, baseline LVEF, NT-proBNP levels, or 6-minute walking distance. With the use of a partial least squares (PLS) predictive model, we identified 9 baseline factors that were associated with both stem cell response and stem cell retention (mechanistic validation). Among the baseline factors positively associated with both clinical response and stem cell retention were G-CSF, SDF-1, LIF, MCP-1, and MCP-3. Among baseline factors negatively associated with both clinical response and retention were IL-12p70, FASL, ICAM-1, and GGT. A decrease in G-CSF at 3-month follow-up was also observed in responders compared with nonresponders (P = .02).
  
  
  CONCLUSIONS
  If further validated, baseline immunologic and nonimmunologic biomarkers may help to identify patients with DCM who are more likely to respond to CD34(+)-based SCT.
authors: Stanford University School of Medicine, Stanford Cardiovascular Institute, Stanford, California; Advanced Heart Failure and Transplantation Center, University Medical Center, Ljubljana, Slovenia.
authors: Francois
authors: F
authors: Haddad
authors: Department of Hematology, University Medical Center, Ljubljana, Slovenia.
authors: Matjaz
authors: M
authors: Sever
authors: Advanced Heart Failure and Transplantation Center, University Medical Center, Ljubljana, Slovenia.
authors: Gregor
authors: G
authors: Poglajen
authors: Department of Nuclear Medicine, University Medical Center, Ljubljana, Slovenia.
authors: Luka
authors: L
authors: Lezaic
authors: Stanford University School of Medicine, Stanford Cardiovascular Institute, Stanford, California.
authors: Philip
authors: P
authors: Yang
authors: Stanford University School of Medicine, Stanford Cardiovascular Institute, Stanford, California.
authors: Holden
authors: H
authors: Maecker
authors: Stanford University School of Medicine, Stanford Cardiovascular Institute, Stanford, California.
authors: Mark
authors: M
authors: Davis
authors: Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors: Tatiana
authors: T
authors: Kuznetsova
authors: Stanford University School of Medicine, Stanford Cardiovascular Institute, Stanford, California.
authors: Joseph C
authors: JC
authors: Wu
authors: Stanford University School of Medicine, Stanford Cardiovascular Institute, Stanford, California; Advanced Heart Failure and Transplantation Center, University Medical Center, Ljubljana, Slovenia. Electronic address: bvrtovec@stanford.edu.
authors: Bojan
authors: B
authors: Vrtovec
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D054377:Chemokine CXCL12 / Q000097:blood*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D053605:Leukemia Inhibitory Factor / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000379:methods; D055414:Myocardial Perfusion Imaging / Q000379:methods; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D019275:Radiopharmaceuticals / Q000494:pharmacology; D013318:Stroke Volume; D019690:Technetium Tc 99m Exametazime / Q000494:pharmacology
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D019275:Radiopharmaceuticals; D018799:Intercellular Adhesion Molecule-1; D016179:Granulocyte Colony-Stimulating Factor; D019690:Technetium Tc 99m Exametazime
keywords: Stem cell therapy; biomarker; dilated cardiomyopathy; heart failure; immunology