Safety and Preliminary Efficacy of Adipose Derived Stem Cells and Low Frequency Ultrasound in PAD

This is a single center, open label, prospective, randomized, controlled study in patients
with non- revascularizable moderate or severe lower extremity PAD receiving autologous stem
cells therapy. We will enroll a maximum of 10 subjects in this study. The patients will be
divided into two groups. One group will receive ADSCs alone and the other group will receive
low frequency ultrasound before the addition of ADSCs. The randomization will be 1:1. If the
results of this pilot study are not clearly different, there will be a need for a phase II
study to support the results.

Baseline, 6 week, 3 month and 6 month assessments of 6 min walking distance, ABIs/TBIs,
TcPO2, Rutherford assessments will be performed for the study group. Prior to the stem cell
treatment, the ultrasound group patient will receive noninvasive transcutaneous pulsed
focused ultrasound around the involved vessel(s) in the affected extremity. All patients will
then receive 100 to 200 million autologous adipose derived stem cell therapy: 1/3 of the
cells will be delivered intra-venous proximal to the lesion (not retrograde), 1/3 of the
cells will be delivered intra- adventitia proximal to the lesion and 1/3 of the cells will be
delivered by intra- muscular injection along the vessel path (20-30 injections each separated
by 1.5 inch). Standard therapy for PAD patients will not be interrupted for the duration of
the study. Standard therapy for PAD is defined as cardiovascular general measures like
lifestyle changes, smoke cessation, exercise, cardiovascular rehabilitation, etc. All
participants have already received maximal non-surgical therapy. Safety will be monitored on
an ongoing basis.

SUBJECT PARTICIPATION A screening evaluation to determine if a potential subject is suitable
for participation in this trial will be conducted prior to enrollment and treatment by the
Investigator. This includes obtaining written informed consent, collection of a complete
medical history, including current and past medications, physical examination and clinical
laboratory tests, PAD related testing (ABI/TBI, 6MWT, TcPO2, QoL questionnaires, etc.).

Eligible subjects will be randomized and treated at the Sponsor hospital as approved by the
sponsor. Study medical staff will evaluate the patients upon admission according to the
scheduled medical assessments to ensure eligibility of the subjects. Ultrasound group will
receive LFUS over the affected limb (see page XIV). Intra-venous, intra-adventitia and
intramuscular dosing of the autologous ADSC will occur on the morning of Day 0. Conscious
sedation (I.V.) may be used during the tissue harvesting and intra-adventitia administration
of the cells.. Subjects must remain in the clinic/hospital until they are clinically stable
for discharge; subjects that are clinically stable will be discharged into the care of a
responsible individual. Follow-up visits will occur at 6 weeks and 3 and 6 months
post-treatment, and may occur with the patient's personal physician who will be provided the
follow-up assessment forms. If this occurs, the Investigator and/or Sponsor or sponsor's
designee may also contact the patient by telephone to collect follow-up safety information.
Adverse events, concomitant medications, vital signs, clinical laboratory test results and
physical examinations will be collected or conducted at follow-up visits according to the
schedule of assessments (Appendix B). All previous medical care, including medications and
rehabilitation, for the patient's current medical conditions will be continued as prescribed
by the patient's personal physician(s). Use of other investigational agents or treatments is
not allowed during this study.

Inclusion Criteria:

1. Males and Females ≥18 years

2. Patients with a Rutherford classification of 3 or 4.

3. Non revascularizable lesions by balloon or stent angioplasty of the lower extremity
SFA (Superficial femoral artery), Popliteal, AT (anterior tibial), PT (posterior
tibial) or peroneal arteries. Non-revascularizable lesions will be determined based on
a CT angiogram and/ or angiography.

4. Life expectancy greater than 6 months.

5. Ability to understand and provide signed informed consent.

6. Reasonable expectation that patient will receive standard post-treatment care and
attend all scheduled safety follow-up visits

7. Written informed consent

Exclusion Criteria:

1. Immunosuppressive agents, including but not limited to, corticosteroids and steroidal
anti- inflammatory agents (SAIDS)

2. Non-steroidal anti- inflammatory agents (NSAIDS)

3. Patients taking currently P2Y12 inhibitors or calcium channel blockers.

4. Uncontrolled seizure disorder

5. Dementia

6. Evidence or presence of immune deficiency.

7. Presence of any other clinically-significant medical condition, psychiatric condition,
or laboratory abnormality that in the judgment of the Investigator or Sponsor would
pose a safety risk to the subject

8. Participation in another study with an investigational drug or device within one month
prior to treatment

9. Females known to be pregnant, lactating or having a positive pregnancy test (will be
tested during screening) or planning to become pregnant during the study

10. Inability to comply with the conditions of the protocol.

11. Allergy to sodium citrate or any "caine" type of local anesthetic