Efficacy and Safety of Umbilical Cord Blood Injection for Critical Limb Ischemia

Umbilical cord blood is a safe alternative source of stem cells used for decades in
hematopoietic stem cell transplants for malignancies. There is also a reported decreased
incidence of acute GVHD compared to matched unrelated donor transplants.A cord blood
registry will be searched for suitable units with compatibility in the ABO and HLA systems.
The minimum total nucleated cell dose required which would be 1.0 x 107/kg, and one unit of
cells will be procured to meet this requirement. Although it is likely that the
transplanted cord blood cells will be rejected over time, we hypothesize that while they
remain in the host's tissue these cells will be producing and releasing cytokines, growth
factors and other humoral factors that might promote vasculogenesis by stimulating
endogenous stem cells and endothelial cells. Since there is no need to collect the patient's
own stem cells, the patient's cardiovascular system will not be subjected to any stress due
to the leukapheresis procedure itself. No injections of exogenous growth factors, which have
been associated with thrombosis, would be required to mobilize the patient's own stem
cells. The procedure could conceivably even be performed in its entirety on an outpatient
basis.

A total of 25 patients will be enrolled in the study. Patients will be followed for 24
months after the procedure with evaluation visits one day after the transplant and then at
one month, six, twelve and twenty four months post-treatment. The visit one day after the
transplant will involve a history and physical with a leg exam, a CBC and a chemistry panel
to evaluate for possible infection, or other adverse event.

Inclusion Criteria:

- Atherosclerotic ischemic peripheral vascular disease or Thromboangiitis Obliterans
with Critical Limb Ischemia (Fontaine stages III and IV)

- Participant must match either a or b

1. Ankle brachial index (ABI) ≤ 0.7

2. Doppler waveforms at posterior tibial artery and dorsalis pedis artery are
monophasic with toe pressure < 30 mmHg.

- A non-surgical candidate for revascularization e.g. prior vascular reconstruction,
inability to locate a suitable vein for grafting, diffuse multi- segment disease, or
extensive infra-popliteal disease not amenable to a vascular graft.

- Age > 18 years old.

- The non-index leg may be treated only in the event and it full fills the same
eligibility criteria and exclusion criteria used in this protocol for the treatment
leg.

- Patients must be on maximal tolerated medical therapy for PVD including A) Cessation
of smoking B) Referral to endocrinologist for control of HgA1c to < 7.0 mg/dl,
control of hyperlipidemia with statins or other anti-hyperlipidemic drugs as
indicated, control of hypertension as indicated C) Antiplatelet therapy with aspirin
and / or cilostazol (unless medically contraindicated, e.g. bleeding or allergy)

Exclusion Criteria:

- Popliteal vascular entrapment syndrome

- Lower extremity infection or infected ulcer

- Hypercoagulable state

- HIV positive

- HBsAg positive

- Uncontrolled arrhythmia, that is, persistence of an arrhythmia despite medical
therapy

- Unstable angina

- Thrombocytopenia < 50,000/ul

- Leukemia or myelodysplasia

- Allergy to E coli or its products

- Patients with metal in their bodies cannot undergo MRIs (MRA). Therefore, patients
with, cochlear implants, or aneurysm clips are not eligible. Coronary artery stents
are not a contraindication. Patients with pacemakers are still candidates provided
they have normal creatinine (< 1.1 mg/dl) and can receive contrast dye (no allergy)
for angiogram instead of MRA. MRI/MRA does not need to be repeated if a prior MRA or
Angiogram Demonstrates inoperable disease.

- Patients who are pregnant

- Poorly controlled diabetes will not be a cause for exclusion but patient must see
endocrinologist for better control

- Current malignancy, except squamous cell or basal cell skin cancers thought to be
easily controlled.

- AST, ALT, or bilirubin more than twice the upper limit of normal.

- WBC < 2.5 / ul.

- Any patient who is actively bleeding, including blood on urine dipstick or fecal
occult blood.

- Patient is on chemotherapy or other immuno-suppressive medications such as steroids,
cellcept, cyclosporine, cytoxan, azathioprine, rituxan, humira or remicade.

- Donor is HLA homozygous and shares that HLA haplotype with the recipient (a different
donor will have to be found)

- Patients diagnosed with Thromboangiitis Obliterans (Buerger's Disease) who are
smokers and are unwilling or unable to quit smoking

- A) Patients with a myocardial infarction within the last 30 days or left ventricular
ejection fraction < 35% B) Patients with a history of malignancy in the last 5 years
(other than basal cell carcinoma or carcinoma in situ) C) Patients with a CVA within
the last 6 months D) Patients with a HbA1c level > 7.0%