title: Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation.
abstract: OBJECTIVE
  We report histological analysis of hearts from patients with end-stage heart disease who were transplanted with autologous skeletal myoblasts concurrent with left ventricular assist device (LVAD) implantation.
  
  
  BACKGROUND
  Autologous skeletal myoblast transplantation is under investigation as a means to repair infarcted myocardium. To date, there is only indirect evidence to suggest survival of skeletal muscle in humans.
  
  
  METHODS
  Five patients (all male; median age 60 years) with ischemic cardiomyopathy, refractory heart failure, and listed for heart transplantation underwent muscle biopsy from the quadriceps muscle. The muscle specimen was shipped to a cell isolation facility where myoblasts were isolated and grown. Patients received a transplant of 300 million cells concomitant with LVAD implantation. Four patients underwent LVAD explant after 68, 91, 141, and 191 days of LVAD support (three transplant, one LVAD death), respectively. One patient remains alive on LVAD support awaiting heart transplantation.
  
  
  RESULTS
  Skeletal muscle cell survival and differentiation into mature myofibers were directly demonstrated in scarred myocardium from three of the four explanted hearts using an antibody against skeletal muscle-specific myosin heavy chain. An increase in small vessel formation was observed in one of three patients at the site of surviving myotubes, but not in adjacent tissue devoid of engrafted cells.
  
  
  CONCLUSIONS
  These findings represent demonstration of autologous myoblast cell survival in human heart. The implanted skeletal myoblasts formed viable grafts in heavily scarred human myocardial tissue. These results establish the feasibility of myoblast transplants for myocardial repair in humans.
authors.affiliation: Section of Cardiac Surgery, University of Michigan, Ann Arbor, MI 48109, USA. fpagani@umich.edu
authors.forename: Francis D
authors.initials: FD
authors.lastname: Pagani
authors.forename: Harout
authors.initials: H
authors.lastname: DerSimonian
authors.forename: Agatha
authors.initials: A
authors.lastname: Zawadzka
authors.forename: Kristie
authors.initials: K
authors.lastname: Wetzel
authors.forename: Albert S B
authors.initials: AS
authors.lastname: Edge
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Jacoby
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Dinsmore
authors.forename: Susan
authors.initials: S
authors.lastname: Wright
authors.forename: Tom H
authors.initials: TH
authors.lastname: Aretz
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Eisen
authors.forename: Keith D
authors.initials: KD
authors.lastname: Aaronson
mesh_terms: D000368:Aged; D001707:Biopsy, Needle; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D006085:Graft Survival; D006353:Heart-Assist Devices; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D032448:Myoblasts, Skeletal / Q000473:pathology* / Q000637:transplantation*; D017202:Myocardial Ischemia / Q000150:complications / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D011336:Probability; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome