Randomized Study of Coronary Revascularization Surgery With Injection of WJ-MSCs and Placement of an Epicardial Extracellular Matrix
Randomized Study of Coronary Revascularization Surgery With Injection of WJ-MSCs and Placement of an Epicardial Extracellular Matrix
Ischemic heart disease is one of the most important causes of mortality and morbidity in the
 Western world and is a public health problem. Among ischemic heart diseases, myocardial
 infarction has specific significance because the cardiac muscle does not have sufficient and
 adequate capacity to regenerate; therefore, necrosis of a region leads to the formation of a
 fibrous scar. Infarction can lead to a progressive and irreversible decrease in cardiac
 function, resulting in heart failure (HF) syndrome, depending on the area affected by this
 scar, via a ventricular remodeling mechanism.

 In recent years, HF has been revealed as a major public health problem due to its incidence
 and its social, economic and especially human impact, as it represents a serious limitation
 of the quality of life of individuals. The prevalence of HF in the general population of the
 United States and the United Kingdom is approximately 1%, and in those older than 75 years,
 the prevalence varies between 5 and 10%. Regarding its prognosis, recent data from the
 Framingham Study indicate that at 5 years, the mortality rate of HF is 75% in men and 62% in
 women; the mean mortality rate of all cancers is 50%.

 The molecular basis of congestive HF is the absence of cardiac cells capable of regenerating
 the heart muscle. Despite the publication of recent studies suggesting the existence of stem
 cells capable of regenerating cardiomyocytes destroyed because of myocardial infarction, in
 humans, the capacity of these cells is insufficient to replace the cells destroyed due to
 necrosis secondary to ischemia.

 In recent years, the accumulation of results derived from preclinical studies has allowed the
 development of the first clinical trials of the feasibility and safety of cardiac
 regeneration using cellular therapy. Several studies have shown that t cells exist in adult
 bone marrow, such as mesenchymal stem cells, hematopoietic stem cells and, more recently,
 multipotent stem cells (MAPC), with the ability to differentiate into endothelial tissue and
 cardiac muscle, which can contribute to the regeneration of damaged myocardial tissue and
 improve cardiac function in animal infarction models. However, cell therapy research has
 moved rapidly toward the use of more undifferentiated cells rather than hematopoietic
 lineages, such as mesenchymal cells. These cells can be obtained from different sources, with
 a tendency toward the use of characterized allogeneic cells, which are immediately available
 in the potential recipient. Given that this type of therapy has not been rigorously
 investigated in Latin America, we aim to determine the effect of therapy using Wharton's
 jelly-derived mesenchymal cells (WJ-MSCs) from the human umbilical cord on neomyogenesis in
 patients with previous myocardial infarction who are undergoing open revascularization. Our
 hospital has some experience with regenerative therapy, both in patients with acute
 myocardial infarction and chronic infarction, with encouraging results that support this new
 phase of inter-institutional research.

 Objective: To evaluate the safety and estimate the effect of coronary revascularization
 accompanied by intramyocardial injection of WJ-MSCs and the placement of an extracellular
 matrix patch seeded with WJ-MSCs compared to coronary revascularization accompanied by
 injection of culture medium without the presence of WJ-MSC and placement of an extracellular
 matrix patch without seeding with WJ-MSC on global and regional cardiac function, myocardial
 viability and the incidence of adverse effects determined as ventricular arrhythmias.
A randomized clinical trial will be conducted as a proof of concept in 40 patients with
 previous myocardial infarction and a viable myocardial zone with indications for coronary
 artery bypass grafts. Twenty patients will be included in each treatment arm over 36 months.
 One group will undergo revascularization surgery, extracellular matrix patch placement and
 injection of cell culture medium; the other group will undergo revascularization surgery,
 extracellular matrix patch placement on the epicardial surface with cultured WJ-MSCs and
 injection of WJ-MSCs around the infarcted zone.

 The allocation of treatments will be defined by block sizes of 2, 4 and 6, randomly
 determined by a random number generator (ralloc, Stata Co. 8,2). This assignment will only be
 known by the tissue bank that will deliver the syringes with the solution to be administered
 and the epicardium patches to the study participants.
Inclusion Criteria:

 -  Patients with a diagnosis of coronary disease, performed by coronary angiography,
 requiring conventional coronary revascularization surgery

 -  History of myocardial infarction; evidence of akinesia or regional dyskinesia more
 than 1 week old

 -  Ejection fraction less than 40%

 -  Age between 30 and 75 years

 -  Negative serology for HIV, hepatitis B virus (HBV), and hepatitis C virus HCV

 -  Negative pregnancy test for women of childbearing age

 -  Patients who sign the informed consent complying with all of the provisions of current
 regulations in Colombia

 Exclusion Criteria:

 -  History of myocardial infarction with ST-segment elevation within 2 weeks prior to
 surgery

 -  History of myocardial infarction without ST-segment elevation within the previous week
 (the decision to include these patients within the first week after suffering a non-ST
 elevation infarction is at the discretion of the research team)

 -  Previous history of tachycardia or ventricular fibrillation

 -  History of active neoplasia or previous chemotherapy treatment

 -  Severe or uncontrolled concomitant disease (i.e., poorly controlled chronic kidney or
 liver failure)

 -  Patients who, due to their place of residence, mental health or social situation, have
 difficulty meeting the conditions of the protocol

 -  Women who are pregnant or breast-feeding

 -  Patients or legal representatives withdrawing informed consent at any time during the
 study.

 -  Previous history of heart transplant

 -  Patients with functional organ impairment: liver function: total bilirubin, aspartate
 aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase
 greater than 2 times the upper reference limit; kidney function: serum creatinine >
 1.5 mg/dl or creatinine clearance < 60 ml/min.