Study of Intracoronary CD34+ Cell Administration in Patients With Early Coronary Atherosclerosis

This is an open label, phase I study to determine safety and efficacy of CD34+ cells in the
treatment and management of CED and early atherosclerosis. Coronary endothelial function will
be assessed in all patients by the administration of intracoronary acetylcholine. Patients
with endothelial dysfunction who meet study inclusion criteria will receive granulocyte cell
stimulating factor (G-CSF), followed by apheresis. The mobilized peripheral cell product will
be processed for selection of CD34+ stem cells, and the purified CD34+ cells will be
administered intracoronary during cardiac catheterization. The patients will undergo repeat
endothelial function assessment 6 months post-procedure, as well as clinical assessments as
described below either via in-person assessment by a nurse or physician, or via phone-call
using a standardized questionnaire at 1, 3, and 6 month follow-up visits. At one month, the
patient will undergo basic laboratory testing including troponin levels, complete blood count
(CBC), electrolyte panel, liver function testing and ECG. At 3 months, the patients will
receive a phone follow-up by the study coordinator who will assess the patient for any
clinical deterioration or significant worsening in symptoms. At 6 months, the patients will
return for a clinical visit, which will include physical examination, basic laboratory
testing and follow-up acetylcholine study with angiography to assess for change in
endothelial function. The first three patients will be sequentially enrolled, and subsequent
enrollment will be held until one month follow-up. Provided there are no safety concerns at
this time, enrollment will continue.

Inclusion Criteria:

- Diagnosis of coronary endothelial dysfunction based on coronary angiogram and
acetylcholine comprehensive coronary physiology study

- Able to provide informed written consent and willing to participate in all required
study follow-up assessments

Exclusion Criteria:

- Acute coronary syndrome or continuous/ongoing chest pain - unremitting and
unresponsive to nitroglycerin or rest - persisting 4 or more days before stent
placement. If the chest pain syndrome is transient and/or intermittent - even if it
began more than 3 days prior to admission - the patient is not excluded.

- Subjects in cardiogenic shock (systolic pressure < 80mm/Hg, on vasopressors or
intraaortic counter pulsation) at the time of consenting. Subjects who recover from
cardiogenic shock by the time of consenting are eligible.

- Subjects unable to receive antiplatelet agents (e.g. aspirin, clopidogrel,
ticlopidine,prasugrel, etc).

- Abnormal laboratory values (Hgb <11 mg/dL; glomerular filtration rate (GFR)<50; liver
function tests (LFTs)>2x upper limit of normal).

- Subjects receiving warfarin who have an international normalized ratio (INR) >2 at the
end of the screening phase or with major bleeding requiring active transfusion
support.

- Subjects with severe cardiac valvular disease expected to undergo surgery within 1
year.

- Subjects with known severe immunodeficiency states (AIDS).

- Significant coronary artery disease on coronary angiogram

- Cirrhosis requiring active medical management.

- Malignancy requiring active treatment (except basal cell skin cancer).

- Subjects with documented active alcohol and /or other substance abuse.

- Females of child bearing potential unless a pregnancy test is negative within 7 days
of the bone marrow harvest.

- Re-occlusion of the infarct related artery (IRA) prior to the infusion procedure.

- Planned revascularization intervention during the next 6 months. (A second PCI can be
performed if done prior to qualifying cardiovascular magnetic resonance imaging (CMR)
at least 96 hours post primary PCI).

- Participation in an ongoing investigational trial.

- Active or suspected bacterial infection requiring systemic intravenous antibiotics.

- Additional factors deemed unsuitable for trial enrollment per discretion of principal
investigator

- Inmates