Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction
Brief Summary: The technique of transplanting progenitor cells into a region of damaged myocardium, termed cellular cardiomyoplasty, is a potentially new therapeutic modality designed to replace or repair necrotic, scarred, or dysfunctional myocardium. Ideally, graft cells should be readily available, easy to culture to ensure adequate quantities for transplantation, and able to survive in host myocardium; often a hostile environment of limited blood supply and immunorejection. Whether effective cellular regenerative strategies require that administered cells differentiate into adult cardiomyocytes and couple electromechanically with the surrounding myocardium is increasingly controversial, and recent evidence suggests that this may not be required for effective cardiac repair. Most importantly, transplantation of graft cells should improve cardiac function and prevent adverse ventricular remodeling. To date, a number of candidate cells have been transplanted in experimental models, including fetal and neonatal cardiomyocytes, embryonic stem cell-derived myocytes, tissue engineered contractile grafts, skeletal myoblasts, several cell types derived from adult bone marrow, and cardiac precursors residing within the heart itself. There has been substantial clinical development in the use of whole bone marrow and skeletal myoblast preparations in studies enrolling both post-infarction patients, and patients with chronic ischemic left ventricular dysfunction and heart failure. The effects of bone-marrow derived mesenchymal stem cells (MSCs) have also been studied clinically.

Currently, bone marrow or bone marrow-derived cells represent highly promising modality for cardiac repair. The totality of evidence from trials investigating autologous whole bone marrow infusions into patients following myocardial infarction supports the safety of this approach. In terms of efficacy, increases in ejection fraction are reported in the majority of the trials.

Chronic ischemic left ventricular dysfunction resulting from heart disease is a common and problematic condition; definitive therapy in the form of heart transplantation is available to only a tiny minority of eligible patients. Cellular cardiomyoplasty for chronic heart failure has been studied less than for acute MI, but represents a potentially important alternative for this disease.


Options:
A: Inclusion Criteria:

* Diagnosis of chronic ischemic left ventricular dysfunction secondary to MI.
* Be a candidate for cardiac catheterization.
* Been treated with appropriate maximal medical therapy for heart failure or post-infarction left ventricular dysfunction.
* Ejection fraction between 20% and 50%.
* Able to perform a metabolic stress test.

Exclusion Criteria:

* Baseline glomerular filtration rate \<50 ml/min/1.73m2.
* Presence of a mechanical aortic valve or heart constrictive device.
* Documented presence of aortic stenosis (aortic stenosis graded as ≥+2 equivalent to an orifice area of 1.5cm2 or less).
* Documented presence of moderate to severe aortic insufficiency (echocardio- graphic assessment of aortic insufficiency graded as ≥+2).
* Evidence of a life-threatening arrhythmia (nonsustained ventricular tachycardia ≥20 consecutive beats or complete heart block) or QTc interval \>550 ms on screening ECG. In addition; patients with sustained or a short run of ventricular tachycardia on ECG or 48 hour Ambulatory ECG during the screening period will be removed from the protocol.
* Documented unstable angina.
* AICD firing in the past 60 days prior to the procedure.
* Be eligible for or require coronary artery revascularization.
* Have a hematologic abnormality as evidenced by hematocrit \< 25%, white blood cell \< 2,500/ul or platelet values \< 100,000/ul without another explanation.
* Have liver dysfunction, as evidenced by enzymes (ALT and AST) greater than three times the ULN.
* Have a coagulopathy condition = (INR \> 1.3) not due to a reversible cause.
* Known, serious radiographic contrast allergy.
* Known allergies to penicillin or streptomycin.
* Organ transplant recipient.
* Clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
* Non-cardiac condition that limits lifespan to \< 1 year.
* On chronic therapy with immunosuppressant medication.
* Serum positive for HIV, hepatitis BsAg, or hepatitis C.
* Female patient who is pregnant, nursing, or of child-bearing potential and not using effective birth control.
B: Inclusion Criteria:

* Diagnosis of dilated cardiomyopathy according to WHO criteria
* Syndromic heart failure in functional class III or IV of the NYHA
* Enrollment and continuous follow-up in cardiac out-patient clinic
* Adequate medical therapy after optimization therapy
* Echocardiogram with an ejection fraction equal to or less than 35% by Simpson's rule

Exclusion Criteria:

* Valvular diseases, except functional mitral or tricuspid reflow
* Coronariography showing a significant lesion (obstruction of at least 50% of the lumen in the troncus or the main arteries - LAD, CX, RC) in one or more arteries
* Serologic diagnosis for Chagas disease or at least two of the following criteria: epidemiology, right bundle branch block, anterior hemi-block, apical aneurism
* Sustained ventricular tachycardia
* Abusive use of alcohol or illicit drugs
* Pregnancy
* Use of cardio toxic drugs
* Any co-morbidity with impact in life expectancy in 2 years
* Renal function compromised (creatinine above 2 mg/dl)
C: Inclusion Criteria:

* Patients presenting to the Heart Attack Centre with acute anterior myocardial infarction (ST elevation in at least 2 contiguous anterior leads ≥ 0.2 mV) and treated with acute PCI with stent implantation within 24 hours after symptom onset
* Acute PCI / stent implantation has been successful (residual stenosis visually \< 30% and TIMI flow ≥ 2).
* At the time of inclusion patient no longer requires i.v. catecholamines or mechanical hemodynamic support (aortic balloon pump)
* Significant regional wall motion abnormality in LV angiogram at the time of acute PCI in the LAD territory
* Age 18 - 80 Years (primary angioplasty confers an adverse prognosis in those over the age of 80 years)
* Written informed consent in the recruiting centres native language

Exclusion Criteria:

* Regional wall motion abnormality outside the area involved in the index acute myocardial infarction
* Need to revascularise additional vessels, outside the infarct artery as a planned procedure (these vessels can be treated at baseline)
* Arteriovenous malformations or aneurysms
* Active infection, or fever or diarrhoea within last 4 weeks
* Chronic inflammatory disease
* Known HIV infection or active hepatitis
* Neoplastic disease without documented remission within the past 5 years
* Cerebrovascular insult within 3 months
* Impaired renal function (creatinine \> 200mmol) at the time of cell therapy
* Significant liver disease (GOT \> 2x upper limit) or spontaneous INR \> 1,5)
* Anemia (hemoglobin \< 8.5 mg/dl)
* Platelet count \< 100.000/µl
* Hypersplenism
* Known allergy or intolerance to clopidogrel, heparin or abciximab
* History of bleeding disorder
* Gastrointestinal bleeding within 3 months
* Major surgical procedure or trauma within 2 months
* Uncontrolled hypertension
* Pregnancy
* Mental retardation leading to inability to obtain informed consent
* Previously performed stem / progenitor cell therapy
* Participation in another clinical trial within the last 30 days
D: Inclusion Criteria:

* Diagnosis of ischemic or nonischemic DCM according to World Health Organization criteria; OR ischemic DCM (DCM in a patient with a history of myocardial infarction or evidence of clinically significant (\>/= 70% narrowing of a major epicardial artery) coronary artery disease)
* No other cardiac surgery or percutaneous cardiac interventions likely to produce clinical improvement, in the opinion of the investigator and the referring interventional cardiologist
* Left ventricular ejection fraction \</= 30% by echocardiogram
* Symptomatic heart failure in NYHA functional class III or IV
* Able to comply with scheduled visits in cardiac out-patient clinic
* Able to tolerate study procedures, including bone marrow aspiration, left lateral thoracotomy or thoracoscopy with single lung ventilation, MRI or cardiac CT, spirometry and 6 minute walk test
* Males and females, 18-86 years of age
* Life expectancy of 6 months or more in the opinion of investigator
* Able to give informed consent
* Normal organ and marrow function (Leukocytes \>/= 3,000/microgram, Absolute neutrophil count \>/= 1,500/microgram, Platelets \>/= 140,000/microgram, AST (SGOT)/ALT (SGPT) \</= 2.5 x institutional standards range) and Creatinine \</= 2.5 mg/dL)
* Adequate pulmonary function (forced expiratory volume in one second \[FEV1\] \> 50% predicted)
* Controlled blood pressure (systolic blood pressure \</= 140; diastolic blood pressure \</= 90 mmHg) and established anti-hypertensive therapy as necessary prior to entry into the study
* Adequate medical management of DCM and other pre-existing conditions. Drug treatment regimen must have been established for at least a month prior to randomization in eligible patients.
* Fertile patients must agree to use an appropriate form of contraception while participating in the study

Exclusion Criteria:

* Severe primary valvular insufficiency(ies)
* Known history of Chronic Obtrusive Pulmonary Disease (Gold stages IIB or more severe only) or restrictive pulmonary disease
* Known history of primary pulmonary hypertension
* Ventricular Assist Device implantation
* Myocardial infarction within 4 weeks of randomization
* Life-threatening ventricular arrhythmia, except if implantable cardioverter defibrillator is implanted
* Unstable angina, characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged duration
* Patients receiving treatment with hematopoietic growth factors
* Patients who require uninterruptible anticoagulation or anti-platelet therapy \[i.e. anticoagulation therapy (e.g. warfarin) that cannot be stopped for 72 hours prior to bone marrow aspiration and intramyocardial injections\]
* Patients receiving anti-platelet therapy (e.g. clopidogrel) that cannot be stopped for 7 days prior to bone marrow aspiration and intramyocardial injections
* Known cancer and undergoing treatment including chemotherapy and radiotherapy
* Patients who will require continuous, systemic, high dose corticosteroid therapy (more than 7.5 mg/day) within 6 months after surgery
* End stage renal disease requiring dialysis
* Patients pregnant or lactating; positive for hCG
* History of alcohol consumption regularly exceeding the equivalent of 2 drinks/day (1 drink = 5 oz of wine or 12 oz \[360mL\] of beer or 1.5 oz \[45mL\] of hard liquor) or history of illicit drug use within 6 months of screening
* Known allergies to protein products (horse or bovine serum, or porcine trypsin)
* Body Mass Index of 40 Kg/m2 or greater
* Patients receiving experimental medications or participating in another clinical study within 30 days of screening
* HIV or syphilis, positive at time of screening
* Active Hepatitis B, or Hepatitis C infection at time of screening
* In the opinion of the investigator, patient is unsuitable for cellular therapy
* Patients receiving anti-angiogenic drugs

Answer: A