title: Transmurality of scar influences the effect of a hybrid-intervention with autologous bone marrow cell injection and aortocoronary bypass surgery (MNC/CABG) in patients after myocardial infarction.
abstract: BACKGROUND
  Cell therapy (CTx) is a strategy to support cardiac regeneration after myocardial infarction (MI). Thus far, clinical studies provided mixed results. Here, we investigated whether transmurality of the infarct may play a relevant role.
  
  
  METHODS
  18 patients (63 ± 3 years, 15 male) undergoing elective coronary artery bypass graft (CABG) surgery 2.2 ± 0.7 months post MI participated. 10 had transmural and 8 non-transmural infarct scars assessed by Tc-99m-MIBI Single-Photon Emission Computed Tomography (SPECT) and F18-FDG-Positron-Emission-Tomography (PET). During surgery, 10 ml of sternal bone marrow were obtained, mononuclear cells (MNC) were isolated. At the end of surgery MNC were injected into the infarctions' center and border zones (10 injections, 2 ml total, 6.6 ± 1.3 × 10(7) MNC).
  
  
  RESULTS
  No major complications attributable to cell therapy were observed. The sizes of non-transmural scars were reduced at 3 and 24 months after treatment (7.7 ± 1.1% and 5.5 ± 1.8 vs. 17.5 ± 4.9%, P=0.05 and P=0.04), while transmural scars remained unchanged (23.5 ± 2.6% and 23.8±3.2 vs. 23.5 ± 2.6%, P>0.99 and P=0.95). A trend towards improved LVEF was seen in patients with non-transmural scars (MRI: 48.8 ± 5.1% vs. 30.6 ± 8.7%, P=0.3; SPECT: 54.1 ± 3.1 vs. 41.0 ± 4.0, P=0.086), but not in patients with transmural scars (MRI: 36.7 ± 3.9 vs. 34.3 ± 5.0, P=0.63, SPECT: 37.8 ± 3.1 vs. 37.9 ± 2.3%, P=0.96).
  
  
  CONCLUSIONS
  A single hybrid intervention of MNC recovery, purification and injection with CABG-surgery (MNC/CABG) may be an attractive modality for cell therapy. However, no regeneration of avital transmural scar tissue seems to occur, while the contribution of MNC to improved perfusion in non-transmural myocardial infarct scars remains to be determined.
authors.affiliation: Department of Internal Medicine III/Cardiology, University of Cologne, Germany. muller.ehmsen@uni-koeln.de
authors.forename: Jochen
authors.initials: J
authors.lastname: Müller-Ehmsen
authors.forename: Paschalis
authors.initials: P
authors.lastname: Tossios
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmidt
authors.forename: Christof
authors.initials: C
authors.lastname: Scheid
authors.forename: Nermin
authors.initials: N
authors.lastname: Unal
authors.forename: Henning
authors.initials: H
authors.lastname: Bovenschulte
authors.forename: Matthias
authors.initials: M
authors.lastname: Hackenbroch
authors.forename: Barbara
authors.initials: B
authors.lastname: Krug
authors.forename: Axel
authors.initials: A
authors.lastname: Goßmann
authors.forename: Uwe
authors.initials: U
authors.lastname: Mehlhorn
authors.forename: Robert H G
authors.initials: RH
authors.lastname: Schwinger
authors.forename: Erland
authors.initials: E
authors.lastname: Erdmann
mesh_terms: D000368:Aged; D016026:Bone Marrow Transplantation / Q000379:methods*; D002921:Cicatrix / Q000000981:diagnostic imaging* / Q000601:surgery*; D001026:Coronary Artery Bypass / Q000379:methods*; D005260:Female; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000601:surgery*; D049268:Positron-Emission Tomography / Q000379:methods; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014182:Transplantation, Autologous / Q000379:methods; D016896:Treatment Outcome