Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS)

Participation in this study will last 18 months. Potential participants will undergo initial
screening 5 to 7 weeks prior to CABG surgery. Screening will include a physical exam, blood
draw, pregnancy test, questions about medical history, current medications, and alcohol or
drug use, an electrocardiogram (ECG), magnetic resonance imaging (MRI) of the heart,
questionnaires, an echocardiogram and a computed tomography (CT) scan. Eligible participants
will then undergo two baseline visits within 6 weeks of their scheduled surgery. Baseline
Visit 1 will consist of vital sign measurements, a bone marrow aspiration to obtain MSCs and
a blood draw for a biomarker test. Baseline Visit 2 will include treadmill test, 6-minute
walk test, pulmonary function (FEV1) study and a 48 Hour Ambulatory ECG. After the second
baseline visit, participants will be assigned randomly to receive either MSCs or placebo
after surgery.

On the day of surgery, once all of the bypass grafts have been placed, a high or low dose of
MSCs or placebo will be injected into a damaged area of the heart that did not receive a
bypass graft. After receiving the injections, participants will remain in the hospital for up
to 7 days. During this stay, participants will undergo a daily blood draw, urine test, ECG,
and ambulatory ECG monitoring for the first 96 hours after surgery.

Upon being discharged, participants will return for monthly visits for 6 months and for
follow-up visits 12 and 18 months after surgery. These visits will repeat most initial
screening and baseline tests. There will be one additional visit 14 days after surgery, which
will include questions about side effects, a physical exam, and a 48-hour ambulatory ECG.

Inclusion Criteria:

- Diagnosis of chronic ischemic heart failure caused by a heart attack

- Scheduled to undergo cardiac surgery for CABG

- Ejection fraction between 15% and 50%

- Presence of an akinetic or dyskinetic region by standard imaging

Exclusion Criteria:

- Glomerular filtration rate of less than 50 mL/min/1.73m2 at study entry

- Contraindication to performance of an MRI scan

- Bone marrow dysfunction, as evidenced by a 20% or more deviation from normal
hematocrit, white blood cell count, or platelet values without another explanation

- A coagulopathy condition not due to a reversible cause (i.e., Coumadin)

- Known, serious radiographic contrast allergy

- Known allergies to penicillin or streptomycin

- Organ transplant recipient

- Clinical history of malignancy within 5 years of study entry (e.g., 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 less than 1 year

- On chronic therapy with immunosuppressant medication

- Serum positive for HIV, hepatitis B, or hepatitis C

- Female who is pregnant, nursing, or of child-bearing potential and not practicing
effective birth control methods