COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

This article published in Cell J (Yakhteh), Vol 20, No 2, Jul-Sep 2018, on pages 267-277, four affiliations (1, 4, 5, and 10) were changed based on authors request.

COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

OBJECTIVES: The regenerative potential of bone marrow-derived mononuclear cells (MNCs) and CD133+ stem cells in the heart varies in terms of their pro-angiogenic effects. This phase II/III, multicenter and double-blind trial is designed to compare the functional effects of intramyocardial autologous transplantation of both cell types and placebo in patients with recent myocardial infarction (RMI) post-coronary artery bypass graft. MATERIALS AND METHODS: This was a phase II/III, randomized, double-blind, placebo-controlled trial COMPARE CPM-RMI (CD133, Placebo, MNCs - recent myocardial infarction) conducted in accordance with the Declaration of Helsinki that assessed the safety and efficacy of CD133 and MNCs compared to placebo in patients with RMI. We randomly assigned 77 eligible RMI patients selected from 5 hospitals to receive CD133+ cells, MNC, or a placebo. Patients underwent gated single photon emission computed tomography assessments at 6 and 18 months post-intramyocardial transplantation. We tested the normally distributed efficacy outcomes with a mixed analysis of variance model that used the entire data set of baseline and between-group comparisons as well as within subject (time) and group×time interaction terms. RESULTS: There were no related serious adverse events reported. The intramyocardial transplantation of both cell types increased left ventricular ejection fraction by 9% [95% confidence intervals (CI): 2.14% to 15.78%, P=0.01] and improved decreased systolic wall thickening by -3.7 (95% CI: -7.07 to -0.42, P=0.03). The CD133 group showed significantly decreased non-viable segments by 75% (P=0.001) compared to the placebo and 60% (P=0.01) compared to the MNC group. We observed this improvement at both the 6- and 18-month time points. CONCLUSIONS: Intramyocardial injections of CD133+ cells or MNCs appeared to be safe and efficient with superiority of CD133+ cells for patients with RMI. Although the sample size precluded a definitive statement about clinical outcomes, these results have provided the basis for larger studies to confirm definitive evidence about the efficacy of these cell types (Registration Number: NCT01167751).

Stem cell research and therapy in the Islamic republic of Iran: pioneering in the Islamic world.

In the early 2000s, the Iranian stem cell research and technology had a relatively strong start that benefited from religious blessings, political and public support, as well as scientific endeavors on the part of non-governmental and public research organizations and universities. Later on, it developed a dynamic niche market of public, private start-up, and spin-off companies and organizations that pioneered in the Islamic world in terms of ISI papers, clinical trials, and cell therapy. However, at present, it faces new challenges stemming from the insufficient finance and a comprehensive law and regulation structure to keep its momentum. To remedy this situation, the scientific community and other stakeholders need to have a series of shared long-time goals and try to build consensus on how to achieve them through nationally approved policy documents.

Five-year follow-up of the local autologous transplantation of CD133+ enriched bone marrow cells in patients with myocardial infarction.

BACKGROUND: The implantation of a CD133+ bone marrow cell population into an ischemic myocardium has emerged as a promising therapeutic modality for myocardial regeneration and restoration of ventricular contractility. While previous studies have documented the short-term safety and efficacy of CD133+ cell transplantation in patients with acute myocardial infarction, there are few reports of long-term follow-up results. Here, we present the results of long-term follow-up of our acute myocardial infarction patients who were treated with intramyocardial injection of CD133+ cells after coronary bypass graft. METHODS: After five years, 13 patients in the cell transplantation group and 5 patients in the control group underwent safety and efficacy investigations by New York Heart Association classification and two-dimensional echocardiography (2D echo). RESULTS: During the five-year study period, no major cardiac adverse events were reported among patients who received CD133+ stem cells. Regarding efficiency, we observed no statistically significant treatment effects for the echocardiographic parameters [left ventricular end-diastolic and end-systolic volumes, and resting ejection fraction] measured during the follow-up period. However, detailed analysis of regional wall motion revealed an improvement in the Wall Motion Score Index from baseline to the six month follow-up, which was maintained during the follow-up period. CONCLUSION: Taken together, the long-term results of the present study indicate that transplantation of CD133+ is a safe and feasible procedure; however, we could not show any major benefits in our patients. Thus, this issue needs to be addressed by conducting other studies with more patients.

Safety analysis and improved cardiac function following local autologous transplantation of CD133(+) enriched bone marrow cells after myocardial infarction.

The CD133(+) bone marrow cell (BMC) population includes primitive multipotent stem cells which induce neoangiogenesis. Studies suggested transplantation of these cells to infarcted myocardium can have a favorable impact on tissue perfusion and contractile performance. We assessed the feasibility, safety and functional outcomes of autologus CD133(+) BMC transplantation during coronary artery bypass grafting (CABG) in patients with recent myocardial infarction. In a prospective, nonrandomized, open-label study, 27 patients with recent myocardial infarction underwent CABG and intramyocardial injection of autologous bone marrow-derived CD133(+) cells (18 patients, BMC group) or CABG alone (9 patients, control group). At 6 months after CABG, the Wall Motion Score Index (WMSI) was significantly reduced for akinetic/dyskinetic segments treated with CD133(+) cells compared with the control group (P<0.006). Likewise, comparison between baseline and follow up results of dobutamine stress echocardiography and myocardial perfusion scintigraphy showed improvement of myocardial viability and local perfusion of the infarcted zone of the BMC group compared with the control group. No complications related to CD133(+) cell transplantation were noted, either procedurally or during postoperative at a mean of 14 months follow up. In patients with recent myocardial infarction, transplantation of CD133(+) cells to the peri-infarct zone during CABG surgery is feasible and safe, with no evidence of early or late adverse events. Moreover, these cells might restore tissue viability and improve perfusion of the infarcted myocardium, suggesting that they may induce myogenesis as well as angiogenesis.