Direct Myocardial Implantation of Human Fetal Stem Cells in Heart Failure Patients: Long-term Results
- 1 February 2010
- journal article
- research article
- Published by Forum Multimedia Publishing LLC in The Heart Surgery Forum
- Vol. 13 (1), 31-5
- https://doi.org/10.1532/hsf98.20091130
Abstract
End-stage heart failure (HF) is refractory to current standard medical therapy, and the number of donor hearts is insufficient to meet the demand for transplantation. Recent studies suggest autologous stem cell therapy may regenerate cardiomyocytes, stimulate neovascularization, and improve cardiac function and clinical status. Although human fetal-derived stem cells (HFDSCs) have been studied for the treatment of a variety of conditions, no clinical studies have been reported to date on their use in treating HF. We sought to determine the efficacy and safety of HFDSC treatment in HF patients. Direct myocardial transplantation of HFDSCs by open-chest surgical procedure was performed in 10 patients with HF due to nonischemic, nonchagasic dilated cardiomyopathy. Before and after the procedure, and with no changes in their preoperative doses of medications (digoxin, furosemide, spironolactone, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, betablockers), patients were assessed for New York Heart Association (NYHA) class, performance in the exercise tolerance test (ETT), ejection fraction (EF), left ventricular end-diastolic dimension (LVEDD) via transthoracic echocardiography, performance in the 6-minute walk test, and performance in the Minnesota congestive HF test. All 10 patients survived the operation. One patient had a stroke 3 days after the procedure, and although she later recovered, she was unable to perform the follow-up tests. Another male patient experienced pericardial effusion 3 weeks after the procedure. Although it resolved spontaneously, the patient abandoned his control tests and died 5 months after the procedure. An autopsy of the myocardium suggested that new young cells were present in the cardiomyocyte mix. At 40 months, the mean (+/-SD) NYHA class decreased from 3.4 +/- 0.5 to 1.33 +/- 0.5 (P = .001); the mean EF increased 31%, from 26.6% +/- 4% to 34.8% +/- 7.2% (P = .005); and the mean ETT increased 291.3%, from 4.25 minutes to 16.63 minutes (128.9% increase in metabolic equivalents, from 2.46 to 5.63) (P < .0001); the mean LVEDD decreased 15%, from 6.85 +/- 0.6 cm to 5.80 +/- 0.58 cm (P < .001); mean performance in the 6-minute walk test increased by 43.2%, from 251 +/- 113.1 seconds to 360 +/- 0 seconds (P = .01); the mean distance increased 64.4%, from 284.4 +/- 144.9 m to 468.2 +/- 89.8 m (P = .004); and the mean result in the Minnesota test decreased from 71 +/- 27.3 to 6 +/- 5.9 (P < .001). Although these initial findings suggest direct myocardial implantation of HFDSCs is feasible and improves cardiac function in HF patients at 40 months, more clinical research is required to confirm these observations.Keywords
This publication has 15 references indexed in Scilit:
- Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: A prospective randomized studyThe Journal of Thoracic and Cardiovascular Surgery, 2005
- Fetal stem cellsBest Practice & Research Clinical Obstetrics & Gynaecology, 2004
- Does the Functional Efficacy of Skeletal Myoblast Transplantation Extend to Nonischemic Cardiomyopathy?Circulation, 2004
- Predictors of mortality in patients with heart failure and preserved systolic function in the Digitalis Investigation Group trialJournal of the American College of Cardiology, 2004
- Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trialThe Lancet, 2004
- Cell transplantation to prevent heart failure: a comparison of cell typesThe Annals of Thoracic Surgery, 2003
- ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure)Circulation, 2001
- Mobilized bone marrow cells repair the infarcted heart, improving function and survivalProceedings of the National Academy of Sciences of the United States of America, 2001
- Bone marrow cells regenerate infarcted myocardiumNature, 2001
- Neovascularization of ischemic myocardium by human bone-marrow–derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac functionNature Medicine, 2001