Protective Effects of Autologous Bone Marrow Mononuclear Cells After Administering t-PA in an Embolic Stroke Model

Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke but poses risk for hemorrhagic transformation (HT). Cell therapy has been investigated as a potential therapy to improve recovery after stroke by the modulation of inflammatory responses and the improvement of blood-brain barrier (BBB) integrity, both of which are associated with HT after t-PA. In our present study, we studied the effect of autologous bone marrow mononuclear cells (MNCs) in an embolic stroke model. We administered MNCs in a rat embolic stroke 2 h after administering t-PA. We observed that even though autologous MNCs did not alter the incidence of HT, they decreased the severity of HT and reduced BBB permeability. One possible mechanism could be through the inhibition of MMP3 released by astrocytes via JAK/STAT pathway as shown by our in vitro cell interaction studies.