Abstract TP108: Ischemia-Induced Multipotent Stem Cells in Human Cerebral Infarction

Abstract

We have previously demonstrated that brain pericytes near cerebral vessels acquired multipotency following cerebral ischemia in mice, and these ischemia-induced multipotent stem cells (iSCs) could contribute to neurogenesis (Nakagomi et al. Eur J Neurosci. 2009, Stem Cells. 2009, 2015). However, it remains unclear whether pericytes can also revert to multipotency in the human brain following stroke. The study protocol was approved by the Ethics Committee of Hyogo College of Medicine. Brain samples were obtained from post-stroke areas in patients requiring both decompressive craniectomy and partial lobectomy for diffuse cerebral infarction (Fig.1). Histological findings of post-stroke human brain tissue sections showed that nestin-positive cells localized near von Willebrand factor-positive endothelial cells and coexpressed pericytic markers (Figs. 2, 3). Then, post-stroke human brain tissue sections were dissociated and cells were incubated under adherent culture conditions. Polymerase chain reaction (PCR) analysis indicated that putative iSCs did not express astrocytic and endothelial lineage markers, but expressed pericytic and neural crest lineage markers. PCR analysis showed that iSCs maintained expression of stem cell and undifferentiated cell markers even after several passages (Fig.4). Immunohistochemistry showed that iSCs differentiated into multiple cells in vitro, including neurons (Fig.5). We demonstrated that iSCs are present within the post-stroke human brain. iSCs can differentiate into neuronal cells and, therefore, might play an important role in central nervous system repair following ischemic stroke.