Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy.

نویسندگان

  • Imran A Memon
  • Yoshiki Sawa
  • Shigeru Miyagawa
  • Satoshi Taketani
  • Hikaru Matsuda
چکیده

OBJECTIVES Cellular cardiomyoplasty with isolated skeletal myoblasts and bone marrow mononuclear cells is an encouraging therapeutic strategy for heart failure. We investigated the achievements accomplished with combined cell therapy of skeletal myoblast and bone marrow mononuclear cell transplantation to the ischemic canine myocardium. METHODS Autologous skeletal myoblasts (1 x 10(8)) and autologous bone marrow mononuclear cells (3 x 10(6)) were injected directly into the damaged myocardium of canine hearts that had undergone 2 weeks of left anterior descending coronary artery ligation. Treatment groups were as follows: skeletal myoblasts plus bone marrow mononuclear cells (combined cell therapy, n = 4), myoblasts (n = 4), bone marrow mononuclear cells (n = 4), and medium only (n = 4). In similarly designed supporting experiments, angiogenic factor expression was evaluated by enzyme-linked immunosorbent assay after cell transplantation in rat hearts that had undergone left anterior descending coronary artery ligation. RESULTS Four weeks after cell implantation, echocardiography demonstrated better cardiac performance with reduced left ventricular dilation and significantly improved ejection fraction in the combined cell therapy group compared with that seen in the other groups (pretreatment, 37.7% +/- 1.1%, vs combined cell therapy, 55.4% +/- 8.6%; myoblasts, 47.4% +/- 7.4%; bone marrow mononuclear cells, 44.4% +/- 6.7%; medium only [control], 34.4% +/- 5.4%; P < .05). A significantly high number of neovessels were observed in the group receiving combined cell therapy only (combined cell therapy, 45.5 +/- 12 x 10(2)/mm2; myoblasts, 26.5 +/- 8 x 10(2)/mm2; bone marrow mononuclear cells, 30.7 +/- 15 x 10(2)/mm2; medium only [control], 7.1 +/- 1 x 10(2)/mm2; P < .05). Immunostained sections expressed the skeletal specific marker myosin heavy chain, although they did not express the cardiac specific marker troponin T. Results of enzyme-linked immunosorbent assay showed the highest expression of vascular endothelial growth factor (combined cell therapy, 2.9 +/- 0.7 ng/g tissue; myoblasts, 0.24 +/- 0.7 ng/g tissue; bone marrow mononuclear cells, 1.9 +/- 0.2 ng/g tissue; medium only [control], 0.19 +/- 0.004 ng/g tissue; P < .05) and hepatocyte growth factor in the combined cell therapy hearts. CONCLUSIONS Combined autologous cellular therapy induced both myogenesis and angiogenesis with enhancement of cardiac performance and reduction of cardiac remodeling, suggesting a capable strategy for treating severe ischemic cardiomyopathy clinically.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The editor's roundtable: advances in stem cell therapy for treatment of cardiovascular disease.

The first clinical trials of stem cell (SC) treatment for cardiac disease in humans, using autologous bone marrow cell transplantation in patients with severe chronic heart failure (HF), were reported in 2002 (using the intracoronary injection route) and in 2003 (using the intramyocardial injection route). Since those initial reports, numerous additional clinical SC trials have been conducted i...

متن کامل

From bench to bedside, work in cell-based myocardial regeneration therapy

In clinical cellular cardiomyoplasty, bone marrow cells and myoblasts are introduced mainly to ischemic cardiomyopathy tissue via several cell delivery systems, such as needle injection or catheter. These clinical studies have demonstrated the safety and feasibility of this technique, but its effectiveness for treating heart failure, especially in the long term, is still under discussion. Neith...

متن کامل

Cellular cardiomyoplasty with autologous skeletal myoblasts for ischemic heart disease and heart failure

Cell transplantation to repair or regenerate injured myocardium is a new frontier in the treatment of cardiovascular disease. Even though it is based on many years of pre-clinical studies, much remains to be understood about this methodology, even as it progresses to the clinic. For example, controversies exist over the specific cells to be used, the dosages needed for tissue repair, how cells ...

متن کامل

The Advancing Field of Cell‐Based Therapy: Insights and Lessons From Clinical Trials

S tem cell therapy aimed at restoring organ function, notably myocardial repair and regeneration postmyocardial infarction (MI), is one of the most exciting and promising frontiers of medical research. While new pharmacotherapies and advances in interventional cardiology have significantly reduced the mortality of ischemic heart disease and heart failure, there remains an ongoing need for innov...

متن کامل

Simultaneous autologous transplantation of cocultured mesenchymal stem cells and skeletal myoblasts improves ventricular function in a murine model of Chagas disease.

BACKGROUND Cellular transplantation is emerging as a promising strategy for the treatment of postinfarction ventricular dysfunction. Whether its beneficial effects can be extended to other cardiomyopathies remains an unexplored question. We evaluated the histological and functional effects of simultaneous autologous transplantation of co-cultured stem cells and skeletal myoblasts in an experime...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of thoracic and cardiovascular surgery

دوره 130 3  شماره 

صفحات  -

تاریخ انتشار 2005