The effects of DPSC-secreted IGF-II on endogenous neuroregeneration

Abstract

Ischemic brain injury is the second leading cause of death worldwide, however, modern medicine is still unable to provide appropriate therapeutics. A promising candidate for stimulating endogenous regeneration are human dental pulp stem cells (hDPSCs). The aim of this study is to evaluate the effects of hDPSC-secreted IGF-II on endogenous regeneration following ischemic stroke. Data showed that CM from hDPSCs contained higher IGF-II levels compared to hBM-MSCs. Additionally, immunocytochemistry confirmed the presence of IGF-IR, IGF-IIR and IR on hBM-MSCs, hDPSCs, HMEC-1, and NSCs. Although there was no impact of IGF-II on NSC proliferation, NSC migration seemed to decrease when IGF-II was neutralized in CM of hDPSCs with an antibody. Regarding the angiogenic potential, IGF-II significantly promoted the number of nodes and meshes in endothelial tube formation. Lastly, dMCAO lesions were characterized by a cortical-restricted infarct, and displayed cell death, tissue degeneration, immune cell infiltration en glial scar formation. Our data suggest hDPSC-secreted IGF-II to play an important role in regulating NSC behavior, neural repair and angiogenesis. Accordingly, future experiments will focus on evaluating regenerative effects of hDPSCs and the contribution of IGF-II in a dMCAO mouse model of ischemic stroke.