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Objective: 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
Conclusion: 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
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Mesenchymal Stem Cells [MSCs] are well known as the regulator of the immune system. These multipotent non-hematopoietic progenitor cells have been originally isolated from bone marrow, and later on found in several other tissues, such as skeletal muscle, umbilical cord blood, adipose and fetal liver tissues. Immunomodulatory effects of MSCs on a variety of immune cells such as T and B lymphocytes, Natural Killer cells [NK], neutrophils, macrophages and dendritic cells, has made a good candidate of them for the treatment of inflammatory disorders, particularly autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. In addition, several studies have indicated mechanisms by which MSCs could reduce immune cell proliferation and activation leading to immune tolerance induction. Since T lymphocytes are considered as the most important immune cells, effect of MSCs on the activity of these cells has a very special significance to direct immune response. Under various conditions, T- lymphocytes have different phenotype and performance and can be differentiated into particular subtype such as regulatory T cells. Both in vitro and in vivo studies have indicated that MSCs modulate innate and adaptive immune system by promoting generation of CD4+CD25+ T regulatory cells which have important role in immune tolerance induction and auto- immune disease prevention. MSCs are able to block pro-inflammatory and increase anti-inflammatory cytokines secretion. So such unique immunomodulatory features make MSCs ideal candidates for clinical application as immunosuppressants which can be considered for autoimmune diseases treatment. Therefore, in this short-review, we attempt to focus mainly on the existing information about MSCs in association with immunomodulatory function of them on the immune system. In addition, the possible mechanisms and the performance impact of MSCs in autoimmune diseases improvement are discussed here. However, increasing knowledge of how MSCs will influence on the immune system suppression, leading us to better use of these cells as a promising tool in the treatment of autoimmune diseases