A Study of Allogeneic Mesenchymal Bone Marrow Cells in Subjects With Ischemic Stroke

Stroke remains a major global healthcare problem. Recent data compiled by the American Heart
Association (AHA) for 2008 show that the annual incidence of new or recurrent stroke in the
United States is about 780,000, with approximately 600,000 of these strokes being first
attacks. Among adults age 20 and older, the estimated prevalence of stroke in 2005 was 5.8
million in the United States, resulting in >150,000 deaths annually, with 4.8 million stroke
survivors alive today. Stroke ranks as the country's third leading cause of death, behind
only cancer and heart disease. The only approved treatments of acute ischemic stroke involve
restoring blood flow to the affected region by using thrombolytics or mechanical devices that
physically remove clots. However, the use of thrombolytics is limited due to the therapeutic
window of < 3-6 hours post onset of stroke symptoms such that only a small fraction of stroke
patients receive this therapy. Following the completion of a stroke, there is little therapy
to offer patients to promote recovery other than physical, occupational, and speech therapy.

Allogeneic mesenchymal stem cells have been used in a number of clinical trials for different
indications demonstrated the safety of allogeneic mesenchymal stem cell treatment. In
addition to their ability to differentiate into multiple different cell types that would be
contributory to the recovery and repair of the brain by replacing destroyed cells,
mesenchymal stem cells also secrete angiogenins, cytokines and trophic factors that can
support and stimulate multiple other cell types. The cascade of cellular events following the
release of these cytokines and trophic factors would also potentially lead to beneficial
effects by restoring blood supply, by rescuing cells at risk, and by stimulating the
remaining cell populations to repair and propagate new cells and synaptic connections.

Inclusion Criteria:

- Clinical diagnosis of ischemic stroke for longer than 6 months

- Brain CT/MRI scan at initial diagnosis and at enrollment consistent with ischemic
stroke

- No substantial improvement in neurologic or functional deficits for the 2 months prior
to enrollment

- NIHSS score between 6-20

- Life expectancy greater than 12 months

- Prior to treatment patient received standard medical care for the secondary prevention
of ischemic stroke

- Adequate organ function as defined by the following criteria:

Exclusion Criteria:

- History of uncontrolled seizure disorder

- History of cancer within the past 5 years.

- History of cerebral neoplasm

- Positive for hepatitis B, C or HIV

- Myocardial infarction withing six months of study entry

- Findings on baseline CT suggestive of subarachnoid or intracerebral hemorrhage within
past 12 months.

- Allergies to Bovine or Porcine products