Please select the eligibility criteria that correspond to the clinical trial below.
Title: MarrOwStim™ PAD Kit for the Treatment of Critical LimB IschemIa (CLI) in Subjects With Severe Peripheral ArteriaL DiseasE (PAD) (MOBILE) - Continued Access
Brief Summary: This study will continue to evaluate the performance of the MarrowStim™ PAD Kit to treat subjects with critical limb ischemia (CLI) caused by severe PAD.


Options:
A: 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.
B: 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
C: Inclusion Criteria:

* Unilateral or bilateral lower extremity ischemia due to advanced peripheral arterial disease
* Unsuitable for revascularization
* Minor tissue loss (Rutherford Category 5) or ischemic rest pain (Rutherford Category 4)
* Competent to give consent
* No current malignancy or history of previous malignancy within the last five years, with the exception of adequately treated non-melanoma skin cancer (evidence of standard preventative cancer screenings required)

Exclusion Criteria:

* Major tissue loss (Rutherford Category 6)
* Diabetics with uncontrolled or untreated proliferative retinopathy
* Poorly controlled diabetes mellitus with HbA1C \> 10%
* Uncompensated congestive heart failure and/or other conditions that preclude general anesthesia
* Myocardial infarction or stroke within last 90 days
* Elevated liver function tests (AST or ALT more than twice the upper limit of normal)
* Renal disease (creatinine \> 2.5 mg/dl) or chronic hemodialysis
* White blood cell count \< 3,000/µL or \> 15,000/µL, platelet count \< 100,000/µL, or hematocrit \< 32%
* Topical growth hormone therapy within last 90 days, or injected growth hormone therapy within last 180 days
* Disease of central nervous system and/or other conditions that impair cognitive function
* Two or more episodes of pulmonary embolus with a documented DVT in index leg or history of DVT in index leg without evidence of clot resolution
* Current infection of index leg
* Pregnant women (negative urine pregnancy test required)
* Lower extremity venous disease with pitting edema in index leg
* Recent history (in the 6 months prior to screening) of bone marrow disease or treatment with any medication or procedure which adversely affects the bone marrow and would prohibit transplantation
* Current osteomyelitis in index leg
* Existing HIV diagnosis
* Organ transplant recipients
* Known terminal disease process with life expectancy less than one year
* Severe concomitant disease(s) or any additional condition(s) which the investigator feels constitute(s) criteria for exclusion of a particular subject
* Major amputation required within 30 days
* Inclusion in any other clinical study that may affect the outcome of this study
* Uncorrected stenosis(es) of greater than 50% in the common and/or external iliac artery and/or common femoral artery of the index leg.
D: Inclusion Criteria:

* Patients 18 years of age or greater with atherosclerotic vascular disease that is viewed as not readily amenable to reconstructive surgery and Rutherford Category 4 ischemia (ischemic rest pain) and Rutherford Category 5 ischemia (ulceration or tissue necrosis) and by the judgment of their referring physician are not reasonable candidates for revascularization options of either percutaneous balloon angioplasty or a surgical revascularization.
* Objective evidence of severe peripheral arterial disease will include an ankle brachial index (ABI) of less than 0.5, or, in the case of patients who have vessels calcified and thereby "non-compressible" vessels metatarsal pulse volume recording (PVR) that is flat or barely pulsatile in the diseased limb on two consecutive examinations performed at least one week apart.
* Patients competent to give informed consent.
* No active malignant disease that could involve the bone marrow, or history of treatment of malignant disease that could have damaged the bone marrow.
* Before being accepted for the study the patient must be screened for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, human transmissible spongiform encephalopathy, including Creutzfeldt-Jacob Disease, Treponema pallidum, and have a negative standard infectious disease panel including a CMV PCR test.
* Patients who are hemodynamically stable.

Exclusion Criteria:

* Patients with poorly controlled diabetes mellitus (HbA1C \> 8%)
* Patients with renal insufficiency (creatinine \> 2.5).
* Patients with evidence of infectious disease as determined by e. above or other medical findings.
* Pregnant women (women capable of childbearing must have a negative pregnancy test).
* Patients with cognitive impairments.
* Other comorbid disease that would be expected to result in less than one year life expectancy
* Past malignancy or history of chemotherapy or radiation affecting the bone marrow.
* History of inflammatory or progressively fibrotic conditions: .e.g., rheumatoid arthritis, systemic lupus erythematosis, vasculitic disorders, idiopathic pulmonary fibrosis, retroperitoneal fibrosis
* Infection as evidenced by WBC count of \>15,000 and/or temperature \>38 degrees C. Large area of cellulitis in the afflicted limb that in the opinion of the investigators would require the institution of antibiotics OR evidence of osteomyelitis corroborated by radiographic or scintigraphic examination
* Cardiovascular conditions:

  * Exercise limiting angina ( Canadian Cardiovascular Society Class 3 (Appendix 7);
  * Congestive heart failure (New York Heart Association class 3 (Appendix 5);
  * Unstable angina;
  * Acute ST elevation myocardial infarction (MI) within 1month;
  * Transient ischemic attack or stroke within 1 month;
  * Severe valvular disease
* Patients with any history of organ transplants;

Answer: C