Please select the eligibility criteria that correspond to the clinical trial below.
Title: Autologous Bone Marrow-derived Mononuclear Cells for Therapeutic Arteriogenesis in Patients With Limb Ischemia A Double Blind, Placebo Controlled, Study in Diabetic and Non-diabetic Patients
Brief Summary: The investigators propose confirm and extend the findings of open studies on the apparent efficacy of bone-marrow derived mononuclear cells for the induction of arteriogenesis in patients with severe claudication or critical leg ischemia and pay special attention to the influence of diabetic disease on the outcome of the study and to the possible pro-atherogenic/ pro-inflammatory effects of BM-MNC injections.


Options:
A: Inclusion Criteria:

* Age \> 18 years
* Severe infra-popliteal peripheral arterial occlusive disease \[PAOD\] (Fontaine class IIb, III or IV)
* Invalidating intermittent claudication, persistent, recurring rest pain requiring analgesia and/or non-healing ulcers present for \> 4 weeks without evidence of improvement in response to conventional therapies
* Ankle brachial index \< 0.6 or "unreliable"
* Not eligible for surgical or radiological revascularization
* Written informed consent

Exclusion Criteria:

* History of neoplasm or malignancy in the past 10 years
* Serious known concomitant disease with life expectancy of less than one year
* Anticipated inability to obtain 100 ml of bone marrow aspirate
* Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus
* Follow-up impossible
B: Inclusion Criteria:

1. Be ≥ 40 and ≤90 years of age.
2. Patients requiring lower extremity major amputation, as determined by an independent vascular specialist.
3. If ulceration or gangrene present, it is distal to malleoli (to allow adequate length of ATM area of approximately 3cm x 10cm x 3 cm)
4. Amputation can safely be performed up to 30 days after screening, as determined by an independent vascular or orthopedic surgeon.
5. Females of childbearing potential must be willing to use one form of birth control for the duration of the study. Female participants must undergo a blood or urine pregnancy test at screening.

Exclusion Criteria:

1. Patients who are pregnant, planning to become pregnant in the next 12 months, or lactating.
2. CHF hospitalization within the last 1 month prior to enrollment.\*
3. Acute coronary syndrome in the last 1 month prior to enrollment.\*
4. HIV positive, or active, untreated HCV as determined by review of medical records.
5. History of cancer within the last 5 years, except basal cell skin carcinoma
6. Inability to provide written informed consent due to cognitive or language barriers (interpreter permitted).
7. Concurrent enrollment in another clinical investigative trial that may alter the outcomes of enrollment in this trial.
8. Any condition requiring immunosuppressant medications (e.g., for treatment of organ transplants, psoriasis, Crohn's disease, alopecia areata).
9. Presence of any clinical condition that in the opinion of the PI or the sponsor makes the patient not suitable to participate in the trial.

   * As defined by the standard definitions of CHF and ACS by the American Heart Association.
C: Inclusion Criteria:

* persistent (\>3 months) disabling claudication (Fontaine's stages IIb or Rutherford's categories 3, viz. pain free walking distance less than 100 meter) despite optimal therapy or critical limb ischemia (Fontaine's stages III/IV or Rutherford's categories 4-6)
* ineligibility for angioplasty or bypass procedures
* male of female, \>18 years old
* life expectancy \> 1 year
* written informed consent

Exclusion Criteria:

* candidates for angioplasty or bypass procedures
* inability to undergo bone marrow harvesting
* any condition in the affected limb that is anticipated to require surgical intervention in the first weeks after BM-MNC treatment
* life threatening co-morbidity
* poorly controlled diabetes (HbA1C \> 10%)
* active malignancy in the 5 years prior to treatment
* INR \>1.5 at the time of bone-marrow harvest
* bleeding diathesis
* inability to undergo arterial catheterization
* inability to follow the protocol and to comply with the follow up requirements
* any other conditions that, in the opinion of the investigators, could interfere with the therapy or could pose a significant threat to the subject if the investigational therapy was to be initiated
D: Inclusion Criteria:

* Diabetes mellitus Type 1 or 2
* Peripheral occlusive arterial disease stage III or IV (Fontaine) with chronical ischemia, chronic foot ulcer, degree of severity \<5 (Wagner), older than 6 weeks, without acute wound infection
* Ulcer size 1 - 30cm2, in case of osteomyelitis only one bone should be affected no trend towards healing in the ulcer after one week of standard treatment
* Angiopathic or angioneuropathic diabetic foot syndrome with no possible option of operative or interventional revascularisation
* Age 18 - 80 years
* Declaration of patient consent

Answer: C