This will be a randomized, placebo-controlled, parallel group, multicenter, Phase III study.The study aims to evaluate the Efficacy, Tolerability and Safety of Intramuscular Injections of PLX PAD for the Treatment of Subjects with Critical Limb Ischemia (CLI) with Minor Tissue Loss (Rutherford Category 5) who are Unsuitable for Revascularization.

Inclusion Criteria:

1. Adult male or female subjects between ages 45-99 years of age.
2. CLI, with minor tissue loss up to the ankle level (Rutherford Category 5)
3. Ankle pressure (AP) ≤70 mmHg or TP ≤50 mmHg in the index leg. (If a subject has ABI >1.4 and TP is not measureable, inclusion may be based on TcPO2 ≤30 mmHg)
4. Subject unsuitable for revascularization (by any method) in the index leg.
5. Ischemic lesions in the index leg stable for at least 2 weeks.
6. Ischemic ulcers in the index leg without tendon or bone exposure (unless secondary to a minor amputation).
7. Under treatment for cardiovascular risk factors: hypertension, hyperlipidemia, diabetes, in accordance with applicable guidelines. Concomitant therapy with a statin and an anti-platelet agent for at least 2 weeks prior to randomization.
8. Women of childbearing potential must have a negative serum pregnancy test at screening and must be willing to use at least one highly effective birth control method throughout the study.
9. Subject understood, agreed and provided informed consent. Patients must give written informed consent before any assessment is performed .

Exclusion Criteria:

1. Non-atherosclerotic PAD (e.g. Buerger's disease).
2. CLI with major tissue loss (Rutherford Category 6) in either leg.
3. Evidence of active infection (e.g., cellulitis, osteomyelitis).
4. Subject having undergone surgical revascularization or major amputation less than 1 month prior to screening, or endovascular revascularization or minor amputation less than 2 weeks prior to screening.
5. Planned or potential need for major/minor amputation or any revascularization within 1 month of study entry upon investigator's judgment.
6. Aorto-iliac stenosis or common femoral artery stenosis ≥70%, or otherwise suspicion of inadequate inflow to the leg.
7. Life expectancy of less than 6 months.
8. Stroke or acute myocardial infarction/unstable angina within 3 months prior to screening.
9. Severe congestive heart failure symptoms (New York Heart Association [NYHA] class III-IV).
10. Uncontrolled severe hypertension.
11. Diabetes mellitus with HbA1c >10%.
12. Current or history of proliferative retinopathy.
13. Known Hepatitis B virus or Hepatitis C virus or acquired immunodeficiency syndrome (AIDS) infections.
14. Subjects with international normalized ratio (INR) >2.
15. Subject on renal replacement therapy or planned to start renal replacement therapy within 3 months of first screening visit.
16. Subject is currently enrolled in, or has not yet completed a period of at least 30 days since ending another investigational device or drug trial(s), unless in long-term follow-up phase.
17. Use of hyperbaric oxygen therapy, prostanoids, spinal cord stimulation, lumbar sympathectomy, wound dressing containing cells or growth factors, or topical platelet derived growth factor.
18. Known allergies to any of the following: DMSO, human serum albumin, bovine serum albumin.
19. History of allergic/hypersensitivity reaction to any substance having required hospitalization and/or treatment with IV steroids/epinephrine.
20. Pulmonary disease requiring supplemental oxygen treatment on a daily basis.
21. Active malignancy or history of malignancy within 5 years prior to study entry.
22. In the opinion of the investigator, the subject is unsuitable for participating in the study.
23. Chronic liver disease Child Pugh class B\C