The Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in Patients Undergoing LVAD Implantation

Intramyocardial injection of mesenchymal precursor cells (MPC) in patients with advanced
heart failure who are treated with left ventricular assist device (LVAD) implantation may
result in a renewable source of proliferating functional cardiomyocytes, as well as induce
development of capillaries and larger size blood vessels to supply oxygen and nutrients to
endogenous myocardium and newly-implanted cardiomyocytes, and release factors capable of
paracrine signaling. If safety is established and an efficacy signal is observed in this
exploratory trial, then the investigators will design a follow-up trial (stage 2) based on
an adaptive design. The next trial would randomize patients to active therapy at one of two
doses (25 and 75 million MPCs) versus placebo, and based on a predetermined selection
criterion drop randomization to one of the dose arms as results accrue. Should this
exploratory trial demonstrate safety but no signal of efficacy, then the subsequent trial
would be based on a single dose of 75 million MPCs versus placebo.

Inclusion Criteria:

- 1. Signed informed consent, inclusive of release of medical information, and Health
Insurance Portability and Accountability Act (HIPAA) documentation; 2. Age 18 years
or older; 3. If the subject or partner is of childbearing potential, he or she must
be willing to use adequate contraception (hormonal or barrier method or abstinence)
from the time of screening and for a period of at least 16 weeks after procedure; 4.
Female subjects of childbearing potential must have a negative serum pregnancy test
at screening; 5. Admitted to the clinical center at the time of randomization; 6.
Clinical indication and accepted candidate for implantation of an FDA approved
implantable, non-pulsatile LVAD as a bridge to transplantation or for destination
therapy.

Exclusion Criteria:

- 1. Planned percutaneous LVAD implantation; 2. Anticipated requirement for
biventricular mechanical support; 3. Cardiothoracic surgery within 30 days prior to
randomization; 4. Myocardial infarction within 30 days prior to randomization; 5.
Prior cardiac transplantation, LV reduction surgery, or cardiomyoplasty; 6. Acute
reversible cause of heart failure (e.g. myocarditis, profound hypothyroidism); 7.
Stroke within 30 days prior to randomization; 8. Platelet count < 100,000/ul within
24 hours prior to randomization; 9. Active systemic infection within 48 hours prior
to randomization; 10. Presence of >10% anti-HLA antibody titers with known
specificity to the MPC donor HLA antigens; 11. A known hypersensitivity to dimethyl
sulfoxide (DMSO), murine, and/or bovine products; 12. History of cancer prior to
screening (excluding basal cell carcinoma); 13. Acute or chronic infectious disease,
including but not limited to human immunodeficiency virus (HIV); 14. Received
investigational intervention within 30 days prior to randomization; 15. Treatment
and/or an incompleted follow-up treatment of any investigational cell based therapy
within 6 months prior to randomization; 16. Active participation in other research
therapy for cardiovascular repair/regeneration; 17. Prior recipient of stem precursor
cell therapy for cardiac repair; 18. Pregnant or breastfeeding at time of
randomization.