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Background. Mesenchymal stem cells (MSCs) express growth factors and other cytokines that stimulate repair and control the immune response. MSCs are also immunoprivileged with low risk of rejection. Umbilical cord-derived MSCs (UCMSCs) are particularly attractive as an off-the-shelf allogeneic treatment in emergency medical conditions. We aim to determine the safety and efficacy of intravenous allogeneic infusion of UCMSCs (CLV-100) by Cytopeutics® (Selangor, Malaysia) in healthy volunteers, and to determine the effective dose at which an immunomodulatory effect is observed. Methodology. Umbilical cord samples were collected after delivery of full-term, healthy babies with written consent from both parents. All 3 generations (newborn, parents, and grandparents) were screened for genetic mutations, infections, cancers, and other inherited diseases. Samples were transferred to a certified Good Manufacturing Practice laboratory for processing. Subjects were infused with either low dose (LD, 65 million cells) or high dose (HD, 130 million cells) of CLV-100 and followed up for 6 months. We measured cytokines using ELISA including anti-inflammatory cytokines interleukin 1 receptor antagonist (IL-1RA), interleukin 10 (IL-10), pro-/anti-inflammatory cytokine interleukin 6 (IL-6), and the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α). Results. 11 healthy subjects (LD, n = 5 ; HD, n = 6 ; mean age of 55 ± 13 years) were recruited. All subjects tolerated the CLV-100 infusion well with no adverse reaction throughout the study especially in vital parameters and routine blood tests. At 6 months, the HD group had significantly higher levels of anti-inflammatory markers IL1-RA ( 705 ± 160 vs. 306 ± 36   pg / mL ; p = 0.02 ) and IL-10 ( 321 ± 27 vs. 251 ± 28   pg / m L; p = 0.02 ); and lower levels of proinflammatory marker TNF-α ( 74 ± 23 vs. 115 ± 15   pg / mL ; p = 0.04 ) compared to LD group. Conclusion. Allogeneic UCMSCs CLV-100 infusion is safe and well-tolerated in low and high doses. Anti-inflammatory effect is observed with a high-dose infusion.

Background: Ischemic cardiomyopathy (ICM) is a leading cause of cardiovascular mortality worldwide. It is defined as abnormal enlargement of the left ventricular (LV) cavity with poor LV function due to coronary artery disease. Currently available established treatments are palliative whereby blood supply is recovered to ischemic regions but fails to regenerate heart tissues. Mesenchymal stem cells (MSCs) offer a promising treatment for ICM given their regenerative and multipotent characteristics. This study aims to investigate the effect of MSCs infusion with concurrent revascularization in patients with severe ICM compared to receiving only revascularization procedure or MSCs infusion.Methods: Twenty-seven patients with history of anterior myocardial infarction (MI) and baseline left ventricular ejection fraction (LVEF) of less than 35% were recruited into this study. Patients who are eligible for revascularization were grouped into group A (MSCs infusion with concurrent revascularization) or group B (revascularization only) while patients who were not eligible for revascularization were allocated in group C to receive intracoronary MSCs infusion. LV function was measured using echocardiography.Results: Patients who received MSCs infusion (either with or without revascularization) demonstrated significant LVEF improvements at 3, 6 and 12 months post-infusion when compared to baseline LVEF within its own group. When comparing the groups, the magnitude of change in LVEF from baseline for third visits i.e., 12 months post-infusion was significant for patients who received MSCs infusion plus concurrent revascularization in comparison to patients who only had the revascularization procedure. Conclusions: MSCs infusion significantly improves LV function in ICM patients. MSCs infusion plus concurrent revascularization procedure worked synergistically to improve cardiac function in patients with severe ICM.

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