This article is more than 5 years old. Information may no longer be current.
Advances in regenerative cardiac cell therapy bode well for heart patients
Researchers continue to increase their knowledge base of regenerative therapies and urge continuation of study.
Click Here to Manage Email Alerts
The results of recent studies have bolstered understanding and given direction to researchers studying both stem cells and the regenerative properties of the heart.
While much of the research into regenerative cell therapy and the use of stem cells to treat various CVDs is still in the experimental phase, more preclinical studies are beginning to emerge suggesting favorable safety and recommending the need for regenerative therapy research to move forward into clinical trials. In particular, the initial positive indicators of using mesenchymal stem cells derived from bone marrow have been topics of interest in the regenerative research community.
Autologous stem cells
A correspondence note from The New England Journal of Medicine highlighted a study in which an arterial blood vessel was grown from a biopsy of a patient’s skin cells; the vessel was strong enough to withstand arterial pressure and function normally. While the study was not powered to apply the results more broadly, the results fit into a growing body of work on regenerative cell therapy.
“I’d call this a potentially exciting anecdotal report,” Douglas Losordo, MD, told Cardiology Today. “Not much information is provided in this non-peer-reviewed letter. The authors describe a tissue-engineered blood vessel used in humans, something that has been sought for some time. Its development from autologous material would be exciting for the reasons stated.” Losordo is a professor of medicine and director of the Feinberg Cardiovascular Research Institute at Northwestern University Medical School and director of the Regenerative Medicine Program at Northwestern Memorial Hospital, Chicago
Losordo and colleagues examined the effects of intramyocardial transplantation of autologous CD34+ stem cells on intractable angina. Patients in the double blind, placebo-controlled randomized trial experienced improvements in different measures of bioactivity.
Angina frequency was monitored at baseline and at three months. After an initial baseline increase in angina frequency in the treatment group of 21.2 ± 16.1 compared with the placebo group (20.5 ± 11.5), angina frequency decreased at three months in the treatment group to 9.6 ± 13.3 episodes compared with 27.0 ± 23.8 episodes in the placebo group. Patients in the treatment group decreased nitroglycerin use at three and six months. Patients treated with CD34+ stem cells also increased exercise tolerance and reported improved quality of life assessments using the Seattle Angina Questionnaire. The results of the phase 1/2a study were published in Circulation.
Mesenchymal stem cells
Particular attention has been paid to mesenchymal stem cells derived from bone marrow. Several studies have demonstrated the relative safety and moderate levels of effectiveness the cells have in improving heart function and treating cardiovascular problems like ischemic heart disease, HF and acute MI.
|
“It’s really a new way to treat heart disease, and we can actually now envision a time where we can restore damaged muscle.”Results from a 2007 meta-analysis of adult bone marrow-derived stem cell studies highlighted the safety of bone marrow stem cell transplantation as well as the extent to which transplantation affected outcomes of patients with ischemic heart disease and acute MI. The meta-analysis reviewed 12 randomized controlled trials and six cohort studies, encompassing a study population of 999 patients. The outcomes that the reviewers were looking for included change from baseline in mean left ventricular ejection fraction, infarct scar size, LV end systolic volume and LV end-diastolic volume. The reviewers concluded that bone marrow stem cell transplantation was “reportedly safe and was associated with modest improvements in LVEF, infarct scar size and LV end systolic volume, beyond those with state-of-the-art therapy,” but reported no significant effect on end LV diastolic volume.
The results of the systematic review and meta-analysis were published in the Archives of Internal Medicine.
Research presented at the 2007 National Heart, Lung, and Blood Institute Symposium on Cardiovascular Regenerative Medicine offered varied new information about the use of mesenchymal stem cells.
Two studies from researchers at The Keck School of Medicine at the University of Southern California, Los Angeles, examined the delivery mechanisms and migration of transplanted mesenchymal stem cells in animal and human models. Those researchers found that although mesenchymal stem cells were associated with improved heart, lung and liver function, the cells would also migrate to different parts of the body regardless of their site of delivery and this affected the efficiency of their regenerative properties.
Another study by researchers at the NHLBI examined the effects of the direct injection of mesenchymal stem cells on transmyocardial revascularization in the porcine model, and found that the delivery technique enhanced the beneficial effects of transmyocardial revascularization.
Ongoing clinical research
A research team led by Joshua Hare, MD, professor of medicine, Miller School of Medicine at the University of Miami and director of the Interdisciplinary Stem Cell Institute, conducted a phase-1 trial assessing the safety of mesenchymal stem cells. The results of the trial were presented at the American College of Cardiology’s Innovation in Intervention Summit in March.
“Our main conclusion of the study was that this should go into clinical trials and into phase-2 as quickly as possible,” Hare told Cardiology Today. “The study showed that there were improvements in the patients’ heart function, lung function and symptom scores. As far as the heart was concerned, it showed beneficial effects both in the function of the heart as well as in the electrical stability of the heart. In total, it was a lot of very exciting information and I think that it bodes very well for the development of this as a therapy.”
Hare was also optimistic about the recent developments and the direction cardiovascular regenerative research has been taking.
“We’ve had a real cap in our armamentarium in cardiology. We haven’t known about the regenerative capacity of the heart, and we haven’t had any therapies to manipulate the regenerative capacity of the heart,” Hare said. “We’ve made huge progress in both of those areas in the last five to six years. It’s really a new way to treat heart disease, and we can actually now envision a time where we can restore damaged muscle.” – by Eric Raible
For more information:
- L’Heureux N, McAllister T. Tissue-engineered blood vessel for adult arterial revascularization. N Engl J Med. 2007;357:1451-1453.
- Losordo D, Schantz R, White C, et al. Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina. Circulation. 2007;115:3165-3172.
- Abdel-Latiff A, Bolli R, Tleyjeh I, et al. Adult bone-marrow-derived cells for cardiac repair: A systematic review and analysis. Arch Intern Med. 2007;167:989-997.
- Dai W, Hale S, Kloner R. The delivery vehicle influences the efficacy of transplanted mesenchymal stem cells’ effect on functional improvement and a rat myocardial infarction model. Abstract presented at: The National Heart, Lung, and Blood Institute Symposium on Cardiovascular Regenerative Medicine; Oct. 2-3, 2007; Bethesda, Md.
- Hale S, Dai W, Dow J, Kloner R. The transmigrating stem cell: Relocation of stem cells injected as therapy for myocardial infarction. Abstract presented at: The National Heart, Lung, and Blood Institute Symposium on Cardiovascular Regenerative Medicine; Oct. 2-3, 2007; Bethesda, Md.
- Zhou Y, Mordini F, Yu Z, Zhang Z. Direct injection of bone marrow-derived adult stem cells improves the beneficial effects of transmyocardial revascularization. Abstract presented at: The National Heart, Lung, and Blood Institute Symposium on Cardiovascular Regenerative Medicine; Oct. 2-3, 2007; Bethesda, Md.
- Hare J. A double-blind, randomized, placebo-controlled clinical trial of allogeneic mesenchymal stem cells for the treatment of patients with acute myocardial infarction. Presented at: the American College of Cardiology Innovation in Intervention Summit; March 24-27, 2007; New Orleans.