Clinical Trials of Cardiac Repair with Adult Bone Marrow- Derived Cells

Abstract

The past decade has witnessed a marked increase in the number of clinical trials of cardiac repair with adult bone marrow cells (BMCs). These trials included patients with acute myocardial infarction (MI) as well as chronic ischemic heart disease (IHD) and utilized different types of BMCs with variable numbers, routes of administration, and timings after MI. Given these differences in methods, the outcomes from these trials have been often disparate and controversial. However, analysis of pooled data suggests that BMC injection enhances left ventricular function, reduces infarct scar size, and improves remodeling in patients with acute MI as well as chronic IHD. BMC therapy also improves clinical outcomes during follow-up without any increase in adverse effects. Although the underlying mechanisms of heart repair are difficult to elucidate in human studies, valuable insights may be gleaned from subgroup analysis of key variables. This information may be utilized to design future randomized controlled trials to carefully determine the long-term safety and benefits of BMC therapy.

Thioredoxin-1 (Trx1) engineered mesenchymal stem cell therapy increased pro-angiogenic factors, reduced fibrosis and improved heart function in the infarcted rat myocardium

“…While still in their infancy, autologous and allogenic MSC therapies, as well as therapies using other bone marrow-derived pluripotent cells, have been proven effective for combating both acute and chronic MI in randomized clinical trials [48]. The mechanisms behind the observed cardioprotection remain debated.…”

“…While pooled analysis suggests a therapeutic benefit, individual basic scientists and clinicians report that these therapies offer no benefit over the protocols already in place. The safety of such therapies, however, appears well-established [48]. Standardization of cell extraction and administration protocols is needed to reach a consensus on the degree of cardioprotection offered by these stem cell therapies.…”

The Angiogenic Paracrine Potential of Mesenchymal Stem Cells

“…Various investigators have continued to assess a large number of cell types injected through several routes to promote cardiac repair in patients with cardiovascular diseases in both the preclinical and clinical stages. Clinical studies have largely been focused on the administration of MSCs [117,118]. For instance, intracoronary injection of bone marrow MSCs led to an improved function of the left ventricle in subjects with acute myocardial infarction [119].…”

Three-Dimensional and Biomimetic Technology in Cardiac Injury After Myocardial Infarction: Effect of Acellular Devices on Ventricular Function and Cardiac Remodelling

“…Regenerative strategies have moved rapidly for clinical application to patients. With aims repair or replacement of dysfunctional substrate, results from various animal models of MI and cardiomyopathy suggest that therapy with adult bone marrow cells (BMCs) improves LV function and atenuate LV remodelling [41]. Moreover, because the basis for improved recovery is unlikely mediated by (re)muscularization of damaged myocardium, the need to evaluate cells capable of diferentiating into contractile tissue has been emphasized.…”