Abstract 97: Intra-Arterial Cell Transplantation Provides Timing-Dependent Cell Distribution and Functional Recovery After Stroke
Background and Purpose— Intra-arterial cell transplantation offers a novel therapeutic strategy for stroke; however, it remains unclear how the timing of cell administration affects cell distribution, brain repair processes and functional recovery. Here, we investigate the hypothesis that the timing of cell transplantation changes the behavior of the cell graft and the host environment in a way that affects functional recovery.
Methods— Rats received human mesenchymal stem cells (hMSCs) via the internal carotid artery at 1, 4 or 7 days (D1, D4 or D7) after middle cerebral artery occlusion and reperfusion. Animals were sacrificed at various time points to assess cell distribution in correlation with the host cerebral hemodynamics, serum levels of matrix metallopeptidase-9 (MMP-9), infiltration of activated microglia, expression of brain derived neurotrophic factor (BDNF), angiogenesis, presence of reactive astrocytes, and neurological recovery.
Results— hMSCs were widely distributed both in the periinfarct and core in D1, and dominantly in the periinfarct in D4, in parallel with the cerebral hemodynamic change. Very few cells were observed in D7. Only in D1 group, the serum level of MMP-9 is significantly lower than that in control group at 72 hours after cell transplantation. At day 7 post-stroke, activation of microglia was significantly suppressed both in the periinfarct and core in D1, and only in the periinfarct in D4. At day 21 post-stroke, BDNF was widely distributed throughout the periinfarct in D1 and D4, and angiogenesis was enhanced. Motor function improved earlier in D1 and later in D4, but only D1 exhibited reduced atrophy.
Conclusions— Our results indicate that intra-arterial cell transplantation provides timing-dependent cell distribution and post-stroke functional recovery via a combination of two mechanisms: neuroprotection and neurorestoration.
- © 2012 by American Heart Association, Inc.