title: Intramyocardial Implantation of bone marrow-derived stem cells enhances perfusion in chronic myocardial infarction: dependency on initial perfusion depth and follow-up assessed by gated pinhole SPECT.
abstract: Cell therapy-induced changes in the perfusion of areas of myocardial infarction (MI) remain unclear. This study investigated whether an original pinhole SPECT technique could be applied to a rat MI model to analyze local improvement in myocardial perfusion relating to engraftment sites of bone marrow-derived stem cells (BMSCs).
  
  
  METHODS
  Four-month-old MI rats were either untreated (n = 8) or treated (n = 10) by intramyocardial injection of (111)In-labeled BMSCs. Early distribution of (111)In-BMSCs within the MI target was evidenced by dual (111)In/(99m)Tc pinhole SPECT 48 h later. Myocardial perfusion was serially monitored by (99m)Tc-sestamibi pinhole gated SPECT up to 3 mo after transplantation.
  
  
  RESULTS
  Forty-eight hours after transplantation, (111)In-BMSCs were observed in all treated rats and in 18 of their 32 underperfused MI segments (<70% sestamibi uptake before transplantation). During the subsequent 3-mo follow-up, the perfusion of MI segments worsened in untreated rats (absolute change in sestamibi uptake, -3% +/- 3%; P < 0.05) but improved in treated rats (+4% +/- 7%; P < 0.05). This perfusion improvement was unrelated to the initial detection of (111)In-BMSCs (+2% +/- 6% in segments with (111)In-BMSCs vs. +5% +/- 7% in those without; not statistically significant) but was strongly associated with less severe perfusion defects before transplantation (+6% +/- 6% in segments with 60%-70% sestamibi uptake [n = 19] vs. -1% +/- 6% in those with <60% uptake [n = 13]; P = 0.003).
  
  
  CONCLUSIONS
  When BMSCs are injected within chronic MI, perfusion enhancement predominates in the MI areas showing a high enough residual perfusion before treatment but not in those of the initial cell engraftment, giving evidence of dependency on the perfusion and metabolic environment at implantation sites.
authors.affiliation: School of Surgery, Faculty of Medicine-UHP, Nancy, France. Nguyen.Tran@medecine.uhp-nancy.fr
authors.forename: Nguyen
authors.initials: N
authors.lastname: Tran
authors.forename: Philippe R
authors.initials: PR
authors.lastname: Franken
authors.forename: Fatiha
authors.initials: F
authors.lastname: Maskali
authors.forename: Joseph
authors.initials: J
authors.lastname: Nloga
authors.forename: Pablo
authors.initials: P
authors.lastname: Maureira
authors.forename: Sylvain
authors.initials: S
authors.lastname: Poussier
authors.forename: Frederique
authors.initials: F
authors.lastname: Groubatch
authors.forename: Chris
authors.initials: C
authors.lastname: Vanhove
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Villemot
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Marie
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002908:Chronic Disease; D003326:Coronary Circulation; D005500:Follow-Up Studies; D006321:Heart / Q000000981:diagnostic imaging*; D007205:Indium Radioisotopes; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D015899:Tomography, Emission-Computed, Single-Photon; D016277:Ventricular Function, Left
chemical_list: D007205:Indium Radioisotopes