Autologous Cell Therapy After Stroke

Stroke remains a leading cause of death and disability. A limited number of therapies, such as intravenous tissue plasminogen activator, have been approved to interrupt stroke in the early hours after symptom onset. Many patients are not able to benefit from these therapies, however, and so a need exists for development of new interventions to reduce disability after stroke. This study will be an early step towards this, and will examine the safety of two cell types, mononuclear cells and marrow stromal cells. In each case, the cells will be autologous, specifically being derived from the subject's own bone marrow.

• autologous bone marrow mononuclear cell transfusion (Biological), also known as mononuclear cells: a single intravenous transfusion approximately 2 days after bone marrow aspiration, and 4 days after stroke onset; the full amount of autologous mononuclear cells derived from 30 cc of bone marrow
• marrow stromal cells (Biological), also known as mesenchymal stromal cells: a single intravenous transfusion approximately 21 days after bone marrow aspiration, and 23 days after stroke onset; the full amount of marrow stromal cells cultured over 21 days from 30 cc of bone marrow (expected to be approximately 1,000,000 cells/kg body weight)
• placebo (Drug): a single intravenous transfusion of saline, approximately 2-21 days after bone marrow aspiration, and 4-23 days after stroke onset; the full amount of mononuclear cells derived from 30 cc of bone marrow

Primary outcomes

• death [90 days after stroke onset]

Secondary outcomes

• myocardial infarction [90 days after stroke onset]
• pulmonary embolism [90 days after stroke onset]
• ischemic stroke [90 days after stroke onset]
• deep venous thrombosis [90 days after stroke onset]
• other arterial or venous thrombosis [90 days after stroke onset]
• Infection requiring IV antibiotics [90 days after stroke onset]

Sex: All, ages: 18 Years to 85 Years

Inclusion Criteria:

* Ischemic stroke that is supratentorial in location and < 72 hours old between stroke onset and bone marrow aspiration
* No major pre-stroke disability
* NIH stroke scale score of 7-24
* Able to undergo bedside bone marrow aspiration
* Age 18-85 years, inclusive
* Reasonable likelihood of receiving standard physical, occupational and speech rehabilitation therapy

Exclusion Criteria:

* No major active hematological, immunological, or oncological diagnoses
* Pregnancy
* Lactating mothers
* At least 24 hours time of any thrombolytic therapy and time of bone marrow aspiration
* Allergy to penicillin or to fetal bovine serum
* Active, major co-existent neurological or psychiatric disease
* Infection with HIV, hepatitis B or C, or syphilis
* Any diagnosis that makes survival to 90 days post-stroke unlikely
* Participation in an experimental therapeutic clinical trial in the prior three months

• Lane TA, Garls D, Mackintosh E, Kohli S, Cramer SC. Liquid storage of marrow stromal cells. Transfusion. 2009 Jul;49(7):1471-81. doi: 10.1111/j.1537-2995.2009.02138.x. Epub 2009 Mar 31. PMID 19389020

• Steven C. Cramer, MD, MMSc, Principal investigator, University of California, Irvine