Dental pulp-derived CD31⁻/CD146⁻ side population stem/progenitor cells enhance recovery of focal cerebral ischemia in rats.

Abstract

Regenerative therapy using stem cells is a promising approach for the treatment of stroke. Recently, we reported that CD31⁻/CD146⁻ side population (SP) cells from porcine dental pulp exhibit highly vasculogenic potential in hindlimb ischemia. In this study, we investigated the influence of CD31⁻/CD146⁻ SP cells after transient middle cerebral artery occlusion (TMCAO). Adult male Sprague-Dawley rats were subjected to 2 h of TMCAO. Twenty-four hours after TMCAO, CD31⁻/CD146⁻ SP cells were transplanted into the brain. Motor function and infarct volume were evaluated. Neurogenesis and vasculogenesis were determined with immunochemical markers, and the levels of neurotrophic factors were assayed with real-time reverse transcription-polymerase chain reaction. In the cell transplantation group, the number of doublecortin-positive cells increased twofold, and the number of NeuN-positive cells increased eightfold, as compared with the control phosphate-buffered saline group. The vascular endothelial growth factor level in the ischemic brain with transplanted cells was 28 times higher than that in the normal brain. In conclusion, CD31⁻/CD146⁻ SP cells promoted migration and differentiation of the endogenous neuronal progenitor cells and induced vasculogenesis, and ameliorated ischemic brain injury after TMCAO.