Conditions

Cardiology

Cardiovascular disease is the leading cause of death worldwide, accounting for more than 17 million deaths per year. Conventional treatments such as surgery and medication have provided some benefit to reduce symptoms, improve clinical indices, slow progression of disease and increase survival. However, despite significant advances in medicine the death toll from cardiovascular disease continues to rise and is expected to grow to more than 23 million by 2030. As such, the search for more effective and safer treatment is on-going among patients, clinicians and researchers.

Stem cell therapy has become a major area of focus in the treatment of various cardiovascular conditions including heart failure, cardiomyopathies, heart attack and others. This is due to the powerful regenerative and anti-inflammatory properties of stem cells in addition to the growing number of human clinical studies showing safety and efficacy.

Stem cells have been shown to have the ability to self-replicate, differentiate into heart muscle cells, prevent fibrosis, reduce inflammation, and induce growth of new blood vessels among other biological effects. These effects have been shown to improve cardiac function and clinical indices, alleviate structural changes in the heart, improve survival and quality of life and reduce occurrence of re-hospitalization.

The vast majority of published clinical studies on stem cell therapy and cardiovascular conditions use stem cells derived from bone marrow tissue. However, due to the invasiveness of the procedure to harvest bone marrow stem cells there is growing interest in other cell types. Umbilical derived stem cells are gaining more attention due to proven efficacy and the ease and accessibility of obtaining such stem cells.

Stem cells can be administered using a variety of methods to treat cardiovascular conditions. The most common methods used in clinical studies include injections into blood vessels of the heart, injections into heart muscles and less commonly intravenous application. However, intravenous delivery of stem cells is gaining more attention due to its ease of application, safety, and efficacy as demonstrated by the RIMECARD trial, a landmark trial of intravenous stem cell therapy and heart failure by Bartolucci et al and the randomized control trial conducted by Butler et al.

Based on early human clinical trials there appears to be a strong argument for the safe and effective use of stem cell therapy in the treatment of cardiovascular disease and heart attack. While we wait for phase II/III trials the current data is encouraging and supports use of stem cell therapy in the clinical setting.

Proven Benefits From Early Human Clinical Trials of Stem Cell Therapy in Cardiovascular Disease and Heart Attack:

Cardiomyopathy

• Improvement in left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic chamber size (LVEDV) in patients with dilated cardiomyopathy (Rong et al)
• Improvement in left ventricular ejection fraction (LVEF) in patients with dilated cardiomyopathy (Rong et al, Jiao et al)
• Significant improvement in left ventricular ejection fraction (LVEF) in patients with non-ischemic dilated cardiomyopathy (Wen et al, Lu et al)
• Significant reduction in mortality rates in patients with non-ischemic dilated cardiomyopathy (Lu et al)
• Improvement in exercise capacity measured by 6 minute walking test (6MWT) in patients with dilated cardiomyopathy (Jiao et al)
• Reduced rate of heart transplantation in patients with dilated cardiomyopathy (Jiao et al)

Heart Failure

• Improvement in left ventricular ejection fraction (LVEF) in patients with heart failure (Jayaraj et al, Bartolucci et al, Wang et al)
• Reduction in overall death rate and hospital readmission in patients with systolic heart failure (Fan et al)
• Improvement in exercise capacity measured by 6 minute walking test in patients with systolic heart failure (Fan et al)
• Reduction in NYHA classification in patients with ischemic heart failure (Fan et al, Wang et al, Bartolucci et al)

Heart Attack

• Improvement in left ventricular ejection fraction (LVEF) in patients with acute heart attack (Lalu et al, Chullikana et al, Hare et al)
• Significant improvement in exercise capacity measured by 6 minute walking test (6MWT) in patients with acute heart attack (Lalu et al)
• Reversed remodeling of left ventricle in patients with acute heart attack (Hare et al)
• Reduction in episodes of ventricular tachycardia and improved pulmonary function tests in patient with acute heart attack (Hare et al)

Specific Conclusions From Selected Systematic Reviews:

“This meta-analysis suggests that stem cell therapy improves left ventricular ejection fraction and reduces left ventricular end-systolic volume and left ventricular end-diastolic chamber size in patients with dilated cardiomyopathy. However, future well-designed large studies might be necessary to clarify the effect of stem cell therapy in patients with dilated cardiomyopathy.”

• Efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy: a systematic appraisal and meta-analysis (Rong et al)

“Results suggest that stem cell therapy was associated with a moderate improvement in LVEF, and the safety analysis indicates no increased risk of mortality in patients with advanced heart failure.”

• Efficacy and Safety of Stem Cell Therapy in Advanced Heart Failure Patients: A Systematic Review with a Meta-analysis of Recent Trials Between 2017 and 2019 (Jayaraj et al)

“Our results suggested that MSC treatment is an effective therapy for HF by improving the prognosis and exercise capacity.”

• Efficacy of mesenchymal stem cell therapy in systolic heart failure: A systematic review and meta-analysis (Fan et al)

“This meta-analysis suggests that stem cell transplantation is a safe and effective treatment option for patients with IHF since SCT resulted in a reduction in the NYHA class, CCS grade, and LVESV, as well as an increase in LVEF, but did not affect mortality.”

• Effect of stem cell transplantation on patients with ischemic heart failure: A systematic review and meta-analysis of randomized controlled trials (Wang et al)

“There was a significant improvement in overall LVEF in patients who received MSCs” and “Results from our systematic review suggest that MSC therapy for ischemic heart disease appears to be safe.”

• Safety and Efficacy of Adult Stem Cell Therapy for Acute Myocardial Infarction and Ischemic Heart Failure (SafeCell Heart): A Systematic Review and Meta-Analysis (Lalu et al)

“Bone marrow-derived mononuclear cells transplantation is associated with a moderate, but significant, improvement in LVEF in patients with nonischaemic DCM.”

Bone marrow-derived mononuclear cell therapy for nonischaemic dilated cardiomyopathy—A meta-analysis (Wen et al)

“Safe delivery of cells has been demonstrated in both preclinical and clinical trials” and “Physicians should be aware of the current status of this treatment so that they can better inform their patients who may be in search of alternative therapies.”

• Adult stem cell therapy and heart failure, 2000 to 2016: A systematic review (Nguyen et al)

“This systematic review and meta-analysis found low-quality evidence that treatment with bone marrow-derived stem/progenitor cells reduces mortality and improves left ventricular ejection fraction over short- and long-term follow-up and may reduce the incidence of non-fatal myocardial infarction and improve New York Heart Association (NYHA) Functional Classification in people with chronic ischaemic heart disease and congestive heart failure.”

• Stem cell therapy for chronic ischaemic heart disease and congestive heart failure. (Fischer et al)

“Bone marrow-derived stem cell therapy might have improved prognoses and appeared to provide moderate benefits in cardiac systolic function at mid-term follow-up.”

• A systematic review of randomised controlled trials examining the therapeutic effects of adult bone marrow-derived stem cells for non-ischaemic dilated cardiomyopathy (Lu et al)

“Our study “demonstrated that stem cell therapy improves cardiac function and reduces mortality in dilated cardiomyopathy patients, which suggested that stem cell therapy may represent a new therapy option for dilated cardiomyopathy.”

• Effects of stem cell therapy on dilated cardiomyopathy (Jiao et al)

Specific Conclusions From Selected Studies:

“Intravenous infusion of UC-MSC was safe in this group of patients with stable heart failure and reduced ejection fraction under optimal medical treatment. Improvements in left ventricular function, functional status, and quality of life were observed in patients treated with UC-MSCs.”

• Safety and efficacy of the intravenous infusion of umbilical cord mesenchymal stem cells in patients with heart failure: A phase 1/2 randomized controlled trial (RIMECARD trial [Randomized clinical trial of intravenous infusion umbilical cord mesenchymal (Bartolucci et al)

“This study shows that despite low myocardial engraftment, intravenously administered MSCs improve clinical end points, effects possibly caused, in part, by systemic anti-inflammatory effects”. “Overall, this study found a single dose of intravenous itMSCs to be safe, to be well-tolerated, and to provide clinically relevant signals for efficacy.”

• Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial (Butler et al)

“[Stem cell] therapy is a reasonable salvage treatment in HF” and due to their small study population “future large scale randomized clinical trials are likely to be designed to elucidate the efficacy.”

• Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial (Fang et al)

“This study showed that Stempeucel was safe and well tolerated when administered intravenously in AMI patients 2 days after percutaneous coronary intervention.”

• Randomized, double-blind, phase I/II study of intravenous allogeneic mesenchymal stromal cells in acute myocardial infarction. (Chullikana et al)

“Intravenous allogeneic hMSCs are safe in patients after acute MI.”

• A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study of Intravenous Adult Human Mesenchymal Stem Cells (Prochymal) After Acute Myocardial Infarction (Hare et al)

For additional information on stem cell therapy in cardiovascular disease and heart attack and more details regarding these studies please visit our Research Archives

Sources:

• Terashvili, M., & Bosnjak, Z. J. (2019). Stem Cell Therapies in Cardiovascular Disease. Journal of Cardiothoracic and Vascular Anesthesia, Vol. 33, pp. 209–222. https://doi.org/10.1053/j.jvca.2018.04.048
• Fan, M., Huang, Y., Chen, Z., Xia, Y., Chen, A., Lu, D., … Ge, J. (2019). Efficacy of mesenchymal stem cell therapy in systolic heart failure: A systematic review and meta-analysis. Stem Cell Research and Therapy, 10(1). https://doi.org/10.1186/s13287-019-1258-1