First-in-human pilot trial of combined intracoronary and intravenous mesenchymal stem cell therapy in acute myocardial infarction

Abstract

BackgroundAcute ST-elevation myocardial infarction (STEMI) elicits a robust cardiomyocyte death and inflammatory responses despite timely revascularization.ObjectivesThis phase 1, open-label, single-arm, first-in-human study aimed to assess the safety and efficacy of combined intracoronary (IC) and intravenous (IV) transplantation of umbilical cord-derived mesenchymal stem cells (UMSC01) for heart repair in STEMI patients with impaired left ventricular ejection fraction (LVEF 30-49%) following successful reperfusion by percutaneous coronary intervention.MethodsConsenting patients received the first dose of UMSC01 through IC injection 4-5 days after STEMI followed by the second dose of UMSC01 via IV infusion 2 days later. The primary endpoint was occurrence of any treatment-related adverse events and the secondary endpoint was changes of serum biomarkers and heart function by cardiac magnetic resonance imaging during a 12-month follow-up period.ResultsEight patients gave informed consents, of whom six completed the study. None of the subjects experienced treatment-related serious adverse events or major adverse cardiovascular events during IC or IV infusion of UMSC01 and during the follow-up period. The NT-proBNP level decreased (1362 ± 1801 vs. 109 ± 115 pg/mL, p = 0.0313), the LVEF increased (52.67 ± 12.75% vs. 62.47 ± 17.35%, p = 0.0246), and the wall motion score decreased (26.33 ± 5.57 vs. 22.33 ± 5.85, p = 0.0180) at the 12-month follow-up compared to the baseline values. The serial changes of LVEF were 0.67 ± 3.98, 8.09 ± 6.18, 9.04 ± 10.91, and 9.80 ± 7.56 at 1, 3, 6, and 12 months, respectively as compared to the baseline.ConclusionThis pilot study shows that combined IC and IV transplantation of UMSC01 in STEMI patients with impaired LVEF appears to be safe, feasible, and potentially beneficial in improving heart function. Further phase 2 studies are required to explore the effectiveness of dual-route transplantation of UMSC01 in STEMI patients.

Synergic Effect of Early Administration of Probiotics and Adipose-Derived Mesenchymal Stem Cells on Alleviating Inflammation-Induced Chronic Neuropathic Pain in Rodents

“…Additionally, abundant evidence has clearly demonstrated that MSCs have the capacity to manage antioxidative stress, perform angiogenesis, and repair damaged tissue and organs, resulting in tissue/organ regeneration as well as improvement of mitochondrial dysfunction [ 25 , 26 , 27 , 29 , 30 ]. Additionally, even allogenic MSCs have been applied for patients with severe cardiovascular disease [ 31 ] or acute respiratory distress syndrome [ 32 ], and the results were reported to be safe and to have potentially improved the clinical outcomes. These findings [ 25 , 26 , 27 , 29 , 30 , 31 , 32 ] highlight that MSC therapy may possess therapeutic potential for NP patients.…”

“…Additionally, even allogenic MSCs have been applied for patients with severe cardiovascular disease [ 31 ] or acute respiratory distress syndrome [ 32 ], and the results were reported to be safe and to have potentially improved the clinical outcomes. These findings [ 25 , 26 , 27 , 29 , 30 , 31 , 32 ] highlight that MSC therapy may possess therapeutic potential for NP patients. However, whether MSC therapy would provide benefits for NP is currently unclear.…”

Effect of Once vs. Twice Intracoronary Injection of Allogeneic-Derived Mesenchymal Stromal Cells after Acute Myocardial Infarction: BOOSTER-TAHA7 Randomized Clinical Trial

“…In an animal study, Gong et al showed that a repeated intravenous dose of human umbilical cord-derived MSCs had a superior therapeutic effect than single-dose treatment in improving the LV function of rats with dilated cardiomyopathy (33). In a groundbreaking phase 1 trial, Hsiao et al found that combined intracoronary and intravenous (two days apart) umbilical cord-derived MSCs appeared to be safe, feasible, and effective (9.80 ± 7.56% rise in EF after 12 months), though con rmatory phase 2 studies are needed (34). On the other hand, we delivered the stem cells via an intracoronary microinfusion, which a meta-analysis revealed to have similar e cacy as a transendocardial injection (23).…”

Whole-Heart Tissue Engineering and Cardiac Patches: Challenges and Promises

“…Yao et al reported that, three months after the first transfer in patients with large MI, repeated bone marrow mononuclear cell infusion through the IC route could improve cardiac function [22]. Hsiao et al showed a reduction of myocardial damage in patients by combining IC and IV administration [23].…”

“…Although the application of melt electrospun scaffolds for engineering is improper for cell encapsulation purposes, foldable PCL melt electrospun hexagonal-shaped scaffolds (8 mm diameter, 300 µm thick) promoted the CM alignment and maturation [51]. Some practical limitations in using electrospinning are the possible toxic effect of remaining chemical ingredients during the electrospinning postprocessing [22], an insufficient mechanical force for load-bearing aims [23], poor cell infiltration and migration of the cells [22,24,52], and the insufficient biochemical complexity of the cardiac ECM [53].…”