Safety Study of Bone Marrow Cell Concentrate Prepared Using the Magellan System to Treat Critical Limb Ischemia (CLI)

Critical limb ischemia (CLI) continues to be an important cause of atherosclerotic morbidity
and mortality despite conventional therapies. Modulation of angiogenesis is a promising
alternative to surgical revascularization. Trials of isolated angiogenic growth factor
therapies using recombinant proteins or gene transfer have been conducted, but with
disappointing results because it is unlikely that a single angiogenic factor is solely or
even primarily responsible for angiogenesis. Emerging stem cell therapies represent a new
approach to the modulation of angiogenesis. Pluripotent hematopoietic stem cells (HSC) hold
promise because they can reproduce a pro-angiogenic milieu in the ischemic limb rather than
upregulate a single angiogenic factor.

For this CLI study, the Magellan® System is utilized for the preparation of autologous cell
concentrate at the point of care. The bone marrow aspirate is obtained from the patient and
concentrated with the cell concentration kit, and delivered intramuscularly to the affected
limb for the treatment of impaired ischemic tissue in order to improve perfusion, reduce
pain and revascularize tissues in patients who have inadequate tissue blood flow,
prohibitive medical comorbidities, or failed previous treatments for revascularization for
the prevention of amputation.

Inclusion Criteria:

- Is able to provide written informed consent prior to study entry

- Is male or female, 18 - 85 years of age

- CLI with rest pain, tissue loss, or gangrene

- No option for revascularization as a result of one of the following:

- failed previous revascularization, such as recurrent instant restenosis or graft
occlusion.

- inadequate target vessels as determined by baseline CTA/angiogram at the time of
enrollment.

- or prohibitive medical comorbidities such as high risk cardiovascular or
pulmonary disease which would restrict operative procedures

- Final determination of no option for revascularization will be made by a
vascular surgeon not associated with the clinical trial.

- ABI less than 0.7, ankle pressure < 50 mmHg, or toe pressure < 30 mmHg.

- TcPO2 < 40 mmHg

- SPP < 35 mmHg

- Female subjects must be of non childbearing potential (defined as postmenopausal for
at least 1 year or surgically sterile [bilateral tubal ligation, bilateral
oophorectomy or hysterectomy]) or must be using adequate contraception (practicing
one of the following methods of birth control):

- Total abstinence from sexual intercourse (minimum of one complete menstrual
cycle before study entry),

- A partner who is physically unable to impregnate the subject (e.g.,
vasectomized)

- Contraceptives (oral, parenteral, or transdermal) for 3 consecutive months prior
to patient's cell concentrate administration,

- Intrauterine device (IUD), or

- Double barrier method (condoms, sponge, diaphragm, or vaginal ring with
spermicidal jellies or cream)

- If female is of childbearing potential, subject must have a negative serum pregnancy
test at screening

- Confirmation of age-appropriate cancer screening consistent with the American Cancer
Society guidelines

Exclusion Criteria:

- Patients with vascular lesions amenable to percutaneous intervention or where
surgical bypass is indicated.

- Any contraindication to stem cell or platelet-rich plasma therapy.

- Isolated aorto-iliac stenoses or occlusions without infra-inguinal disease.

- Pregnancy

- Hemoglobin A1c >10 % on day of enrollment.

- Have an active malignancy or have undergone treatment for a malignancy in the
preceding 5 years, with the exception of successful treatment of non-melanoma skin
cancer.

- Stage 4 or greater chronic kidney disease (eGFR < 30 ml/min, MDRD estimate)

- Hemoglobin < 10 g/dl.

- Thrombocytopenia < 100,000 platelets/µL.

- Unwilling or unable to comply with follow-up visits.

- Proliferative retinopathy as determined by baseline retinal exam.

- Is unable to refrain from nicotine, caffeine and alcohol for a period beginning 24
hours prior to the treatment visit

- Has received an investigational medication or other study trial participation within
30 days prior to the Treatment Visit