title: 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.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, Krakow, Poland ; Clinical Departments, John Paul II Hospital, Krakow, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Musialek
authors.affiliation: Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, Krakow, Poland ; Clinical Departments, John Paul II Hospital, Krakow, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Mazurek
authors.affiliation: Department of Transplantation, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Jarocha
authors.affiliation: Clinical Departments, John Paul II Hospital, Krakow, Poland ; Department of Interventional Cardiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Tekieli
authors.affiliation: Nuclear Imaging Laboratory, John Paul II Hospital, Krakow, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Szot
authors.affiliation: Clinical Departments, John Paul II Hospital, Krakow, Poland ; Nuclear Imaging Laboratory, John Paul II Hospital, Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kostkiewicz
authors.affiliation: Magnetic Resonance Imaging Laboratory, John Paul II Hospital, Krakow, Poland.
authors.forename: R Pawel
authors.initials: RP
authors.lastname: Banys
authors.affiliation: Magnetic Resonance Imaging Laboratory, John Paul II Hospital, Krakow, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Urbanczyk
authors.affiliation: Department of Interventional Cardiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kadzielski
authors.affiliation: Clinical Departments, John Paul II Hospital, Krakow, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Trystula
authors.affiliation: Department of Transplantation, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Kijowski
authors.affiliation: Clinical Departments, John Paul II Hospital, Krakow, Poland ; Department of Interventional Cardiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Zmudka
authors.affiliation: Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, Krakow, Poland ; Clinical Departments, John Paul II Hospital, Krakow, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Podolec
authors.affiliation: Department of Transplantation, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Majka
keywords: Wharton's jelly mesenchymal stem cells; acute myocardial infarction; feasibility; first-in-man; human umbilical cord matrix; myocardial regeneration; safety