Abstract 139: Which Cell Populations Within The Mononuclear Fraction Of Bone Marrow Contribute To The Beneficial Effects Of Autologous Bone Marrow Cell Therapy For Stroke
Background: Bone marrow derived mononuclear cells (MNCs) enhance recovery after acute stroke in animal models and clinical trials are testing MNCs in stroke patients. MNCs are composed of a mixture of various cell populations. We aimed to determine which cell populations within MNCs contribute to their beneficial effects in stroke.
Methods: Male SV129 mice were subjected to transient CCAo/MCAo for 90 minutes. After 24hrs, animals were randomly assigned to 6 groups: 1) Saline; 2) Whole MNCs; 3) MNCs depleted of lymphoid cells; 4) MNCs depleted of myeloid cells; 5) MNCs depleted erythroid cells; 6) MNCs depleted of stem cells (n=5 per group). Bone marrow was harvested and MNCs were isolated. In group 2, the whole MNC fraction was dosed at 1.5 million cells per animal IV. The amount of cells administered in groups 3 to 5 was the same dose of MNCs as in group 2 minus the specific fraction depleted. At day 3 after stroke, all animals were sacrificed. Serum was collected for Multiplex assay. Brains were harvested to evaluate the infarction sizes with TTC.
Results: MNCs reduced infarct maturation compared with saline. The depletion of lymphoid, myeloid, or stem cell populations from the whole fraction of MNCs significantly attenuated or abolished the cytoprotective effect. Only the depletion of erythroid cells had no effect on lesion size. In addition, animals treated with MNCs have a profound effect on a range of inflammatory cytokines. Serum IL-1β is reduced while IL-10 is increased. The depletion of different fractions of cells changes the inflammatory profile, e.g., an increase in IL-1β and a decrease in IL-10 when lymphoid cells were depleted.
Conclusions: Different cell subpopulations from different lineages within MNCs are required to reduce infarct maturation in the post-ischemic brain. We are determining if depletion of these different fractions has an impact on behavioral outcomes. In addition, IL-10 may be an important cytokine underlying the cytoprotective effects of MNCs.
- © 2012 by American Heart Association, Inc.