BM-MNCs for Lower Extremity Compartment Syndrome Injury

The primary objectives are to assess safety and tolerability of a high and low dose of
autologous bone marrow mononuclear cells. Secondary objectives include evaluation of
potential responses of the BM-MNC therapy.

This is a two-stage, randomized, unblinded, multicenter (two sites), controlled phase 1
clinical trial to evaluate the safety of two different doses of intramuscular injections of
autologous bone marrow mononuclear cells, commonly known as a type of stem cell. Acute
compartment syndrome injury is a mixed soft tissue injury due to a trauma that causes edema
leading to excessive pressure in the muscle compartment. This type of injury frequently
results in permanent reduction in function and disability.

A total of 18 participants that have undergone a fasciotomy for treatment of a lower leg
compartment syndrome will be enrolled with 6 assigned to the control (observational) group, 6
to the low cell-dose group and 6 to the high cell-dose group. The treatment arm will receive
a single dose (high or low) of autologous BM-MNCs 5 - 9 days post injury and fasciotomy and a
minimum of 3 months of standard of care physical rehabilitation. An observational control arm
will not receive cells post fasciotomy but will undergo a standard of care course of physical
therapy and will be followed for comparison to assess early safety signals and potential
benefit.

Inclusion Criteria:

- Females and males 18 - 70 years old

- Has single or multiple compartment syndrome of the lower leg that includes the
anterior tibial compartment

- Trauma patients with lower extremity CS requiring fasciotomy that can be treated with
autologous BM-MNC therapy on day 5-9 post-fasciotomy

- Healthy contralateral lower extremity for comparison testing

- Ability to sign an informed patient consent form

- Access and willingness to complete a standard of care course of rehabilitation therapy
and 24 months follow-up evaluations

- Have sufficient skin to allow for tissue approximation for wound closure

- Anterior compartment muscle volume between 200 - 280 cc as determined by MRI/CT

- Within the institutions' clinical reference ranges for screening laboratory panels:
CBC with differential, Prothrombin time/PTT/INR, liver function tests, HbA1C, and
serum creatinine;

- Negative HIV test

- Female subjects must be of non-childbearing potential or must be using adequate
contraception

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

- Willing and able to adhere to the study schedule

Exclusion Criteria:

- Prior compartment syndrome of same limb;

- Active malignancy or has undergone treatment for a malignancy in the preceding 5 years
as indicated in past medical history or self-report if medical records do not
accompany subject or are unable to be collected (basal cell carcinoma
non-exclusionary);

- HIV positive as indicated by past medical history, self-report, or positive HIV test;

- Diagnosis of Type 1 or Type 2 diabetes as indicated by past medical history,
self-report, or elevated HbA1C consistent with diabetes;

- Diagnosis of chronic lower extremity vascular disease as diagnosed by current
physician diagnosis, indicated in past medical history, or self-report if medical
records do not accompany subject or are unable to be collected;

- Patients unable to sign an informed patient consent;

- Anticipated amputation of involved limb or contralateral limb precludes comparison
studies; significant injury to contralateral limb that would preclude comparative
testing;

- Spinal cord injury

- Moderate to severe traumatic brain injury defined as a loss of consciousness for more
than 30 minutes and/or an abnormal brain MRI/CT scan;

- Current systemic infection;

- Local infection of the involved muscle group;

- Use of ventilator that would preclude rehabilitation protocols;

- Lack of access or unwillingness to complete standard of care course of physical
therapy rehabilitation;

- Life expectancy 12 months or less;

- Bone marrow disorders (i.e. leukemia, aplastic anemia, lymphoma) ;

- Insufficient skin for tissue approximation for wound closure or lower extremity burns
that may affect wound closure;

- Significant tissue loss in involved muscle(s) (i.e., extensive debridement such that
there is insufficient residual tissue for stem cell administration and subsequent
engraftment);

- Lower extremity compound fracture;

- Anterior tibialis muscle volume less than 200 cc or greater than 280 cc as determined
by MRI/CT;

- Evidence of any past or present clinically significant medical condition that would
impair wound healing

- History or clinical manifestations of significant renal, hepatic, cardiovascular,
metabolic, neurologic, psychiatric, or other condition that would preclude
participation in the study as determined by the investigator or the investigator's
designee;

- Any reason, considered by the principal investigator or designee, to preclude subject
enrollment in the study that might represent a threat to the subject's health or
safety.