title: Phase I Clinical Trial of Autologous Stem Cell-Sheet Transplantation Therapy for Treating Cardiomyopathy.
abstract: BACKGROUND
  When transplanted into failing heart, autologous somatic tissue-derived cells yield functional recovery via paracrine effects that enhance native regeneration. However, the therapeutic effects are modest. We developed a method in which scaffold-free cell sheets are attached to the epicardial surface to maximize paracrine effects. This Phase I clinical trial tested whether transplanting autologous cell-sheets derived from skeletal muscle is feasible, safe, and effective for treating severe congestive heart failure.
  
  
  RESULTS
  Fifteen ischemic cardiomyopathy patients and 12 patients with dilated cardiomyopathy, who were in New York Heart Association functional class II or III and had been treated with the maximum medical and/or interventional therapies available, were enrolled. Scaffold-free cell sheets of 3 to 9×108cells derived from autologous muscle were transplanted over the LV free wall via left thoracotomy, without additional interventional treatments. There were no procedure-related major complications during follow-up. The majority of the ischemic cardiomyopathy patients showed marked symptomatic improvement in New York Heart Association classification (pre: 2.9±0.5 versus 6 months: 2.1±0.4,P<0.01; 1 year: 1.9±0.3,P<0.01) and the Six-Minute Walk Test with significant reduction of serum brain natriuretic peptide level (pre: 308±72 pg/mL versus 6 months: 191±56 versus 1 year: 182±46,P<0.05), pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vein resistance, and left ventricular wall stress after transplantation instead of limited efficacy in dilated cardiomyopathy patients.
  
  
  CONCLUSIONS
  Cell-sheet transplantation as a sole therapy was feasible for treating cardiomyopathy. Promising results in the safety and functional recovery warrant further clinical follow-up and larger studies to confirm this treatment's efficacy for severe congestive heart failure.
  
  
  BACKGROUND
  URL: http://www.umin.ac.jp/english/. Unique identifier: UMIN000003273.
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Domae
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yoshikawa
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Teruya
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Medical Innovation, Medical Center for Translational and Clinical Research, Osaka University Hospital, Osaka, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Saito
authors.affiliation: Department of Cardiology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sakata
authors.affiliation: Department of Radiology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Seiki
authors.initials: S
authors.lastname: Hamada
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Toda
authors.affiliation: Department of Clinical Medicine, School of Pharmacy Kitasato University, Tokyo, Japan.
authors.forename: Kyongsun
authors.initials: K
authors.lastname: Pak
authors.affiliation: Department of Clinical Medicine, School of Pharmacy Kitasato University, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan sawa-p@surg1.med.osaka-u.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D000328:Adult; D000368:Aged; D062186:Arterial Pressure; D009202:Cardiomyopathies / Q000209:etiology / Q000628:therapy; D002311:Cardiomyopathy, Dilated / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications; D011651:Pulmonary Artery; D011667:Pulmonary Veins; D011669:Pulmonary Wedge Pressure; D033581:Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014655:Vascular Resistance; D000070857:Walk Test
keywords: autologous stem cell‐sheet; cellular transplantation; ejection fraction; growth factors and cytokines; ischemic cardiomyopathy; myocardial regeneration