Myocardial regeneration strategy using Wharton's jelly mesenchymal stem cells as an off-the-shelf 'unlimited' therapeutic agent: results from the Acute Myocardial Infarction First-in-Man Study

Piotr Musialek; Adam Mazurek; Danuta Jarocha; Lukasz Tekieli; Wojciech Szot; Magdalena Kostkiewicz; R Pawel Banys; Malgorzata Urbanczyk; Andrzej Kadzielski; Mariusz Trystula; Jacek Kijowski; Krzysztof Zmudka; Piotr Podolec; Marcin Majka

doi:10.5114/pwki.2015.52282

Myocardial regeneration strategy using Wharton's jelly mesenchymal stem cells as an off-the-shelf 'unlimited' therapeutic agent: results from the Acute Myocardial Infarction First-in-Man Study

Postepy Kardiol Interwencyjnej. 2015;11(2):100-7. doi: 10.5114/pwki.2015.52282. Epub 2015 Jun 22.

Affiliations

¹ Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, Krakow, Poland ; Clinical Departments, John Paul II Hospital, Krakow, Poland.
² Department of Transplantation, Jagiellonian University Medical College, Krakow, Poland.
³ Clinical Departments, John Paul II Hospital, Krakow, Poland ; Department of Interventional Cardiology, Jagiellonian University Medical College, Krakow, Poland.
⁴ Nuclear Imaging Laboratory, John Paul II Hospital, Krakow, Poland.
⁵ Clinical Departments, John Paul II Hospital, Krakow, Poland ; Nuclear Imaging Laboratory, John Paul II Hospital, Krakow, Poland.
⁶ Magnetic Resonance Imaging Laboratory, John Paul II Hospital, Krakow, Poland.
⁷ Department of Interventional Cardiology, Jagiellonian University Medical College, Krakow, Poland.
⁸ Clinical Departments, John Paul II Hospital, Krakow, Poland.

Abstract

Introduction: In large-animal acute myocardial infarction (AMI) models, Wharton's jelly (umbilical cord matrix) mesenchymal stem cells (WJMSCs) effectively promote angiogenesis and drive functional myocardial regeneration. Human data are lacking.

Aim: To evaluate the feasibility and safety of a novel myocardial regeneration strategy using human WJMSCs as a unique, allogenic but immuno-privileged, off-the-shelf cellular therapeutic agent.

Material and methods: The inclusion criterion was first, large (LVEF ≤ 45%, CK-MB > 100 U/l) AMI with successful infarct-related artery primary percutaneous coronary intervention reperfusion (TIMI ≥ 2). Ten consecutive patients (age 32-65 years, peak hs-troponin T 17.3 ±9.1 ng/ml and peak CK-MB 533 ±89 U/l, sustained echo LVEF reduction to 37.6 ±2.6%, cMRI LVEF 40.3 ±2.7% and infarct size 20.1 ±2.8%) were enrolled.

Results: 30 × 10(6) WJMSCs were administered (LAD/Cx/RCA in 6/3/1) per protocol at ≈ 5-7 days using a cell delivery-dedicated, coronary-non-occlusive method. No clinical symptoms or ECG signs of myocardial ischemia occurred. There was no epicardial flow or myocardial perfusion impairment (TIMI-3 in all; cTFC 45 ±8 vs. 44 ±9, p = 0.51), and no patient showed hs-troponin T elevation (0.92 ±0.29 ≤ 24 h before vs. 0.89 ±0.28 ≤ 24 h after; decrease, p = 0.04). One subject experienced, 2 days after cell transfer, a transient temperature rise (38.9°C); this was reactive to paracetamol with no sequel. No other adverse events and no significant arrhythmias (ECG Holter) occurred. Up to 12 months there was one new, non-index territory lethal AMI but no adverse events that might be attributable to WJMSC treatment.

Conclusions: This study demonstrated the feasibility and procedural safety of WJMSC use as off-the-shelf cellular therapy in human AMI and suggested further clinical safety of WJMSC cardiac transfer, providing a basis for randomized placebo-controlled endpoint-powered evaluation.

Keywords: Wharton's jelly mesenchymal stem cells; acute myocardial infarction; feasibility; first-in-man; human umbilical cord matrix; myocardial regeneration; safety.