Factors affecting neurogenesis after application of human mesenchymal stem cells in ischemic rat model

Abstract

"Background: We recently reported the results of clinical trial of ex vivo culture expanded autologous mesenchymal stem cells (MSCs) in patients with severe ischemic stroke. We proposed that an optimal condition, for either donor or recipient, may exist and enhance the effects of the mesenchymal stem cells in those patients. Thus we evaluated the effect of the MSCs in impacts on the neurogenesis depending on the passage of MSCs.

Methods and Results: We performed immunohistochemical studies and behavioral tests in transient middle cerebral occlusion rat model. Intravenous application of ex vivo cultured human mesenchymal cells, earlier (passage 2) or later (passage 6), was performed in stroke rat model. Compared to rat received later passage MSCs, neurogenesis revealed by bromodeoxyuridine staining was more pronounced in rat received early passage MSCs (P<0.05). Double staining showed that neuroblast (bromodeoxyuridine positive cells), but not MSCs (human nuclei matrix antigen positive cells), expressed neuronal and glial phenotypes.

Conclusions: Our results indicated that ischemia-induced neurogenesis was enhanced by the application of mesenchymal stem cells, this process was related to the passage of ex vivo stem cell culture."