gms | German Medical Science

Objective: Ischemic stroke accounts for ~80% of all cases presented. Currently, mechanical recanalization and thrombolysis are the only available short-term therapies available. Numerous experimental studies have shown a functional improvement after stem cell administration during the acute phase. However, the time course and cellular mechanisms of these processes are not yet fully understood. The influence of stem cells in these processes is equally obscure. A better understanding of the mechanisms involved should contribute to the optimization of cell therapy for stroke patients. The aim of this project was to compare the impact of intracerebral versus intravenous administration of human marrow stromal cell (MSCs) after a transient middle cerebral artery occlusion (MCAO) in rats and to correlate these effects with functional recovery.

Method: 44 male Sprague-Dawley (3–4 months, 350–449 g) rats were used in this study. Rats were divided into four cohorts: 1) MCAO lesion only, 2) MCAO plus IV delivery of MSCs, 3) MCAO plus stereotactic delivery of MSCs, and 4) sham. MRI was performed 48 h after MCAO in order to evenly distribute the rats within the groups according to infarct size. Each experimental group had 13 rats and the sham group had 5 rats. 12 of 39 rats did not survive beyond 72 h after the MCAO. This corresponds to a mortality rate of 31%. Only rats surviving the entire follow-up period were included in the analyses. Behavioral tests were conducted 1 week before and at 3, 5, 7, and 9 weeks after transient MCAO. Each behavioral battery of tests consisted of three motoric elements (cylinder, accelerated rotarod, Swedish ladder). Additionally, weight was monitored weekly throughout the study.

Results: Immunohistochemical analysis identified MSCs, which have migrated to the site of injury. Behavioral results indicate improved functional recovery in the MSC treated groups, as compared to the lesion only group. No significant differences between local and systemic application of MSCs was evident.

Conclusions: There were no apparent differences observed in this study between experimental groups, which received either intracerebral (STX) or systemic (IV) transplants. This indicates that systemic application is a viable alternative in cell therapy.