Angiogenesis promotion of the transplantation of human amniotic mesenchymal stem cells via the Ang-1/Tie-2 signaling pathways in Alzheimer's disease model

Background Alzheimer's disease (AD) is a progressive degenerative disease of the central nervous system, leading to cognitive decline, mental symptoms, and behavioral disorders. The comorbidity of cerebrovascular disease in AD patients will accelerate the development of cognitive impairment and dementia. Since the dysfunction of the cerebral vasculature is closely related to neuropathology in AD patients, the protection of cerebral microvascular function and the improvement of cerebral microcirculation may bring a potential path for AD treatment. Human amniotic mesenchymal cells (hAMSCs) as a more advantageous cellular therapy for AD are proven to improve AD model mice's learning and memory abilities significantly, but fewer studies on angiogenesis and blood-brain barrier recovery have been found. Objective The study aimed to analyze the changes in angiogenesis-related factors of hAMSCs transplantation in the AD model and explore the underlying molecular mechanism. Methods hAMSCs were injected into APP/PS1 and wild type (WT) mice via tail vein, and the hAMSCs distribution in the cerebral tissue and angiogenesis in the hippocampal tissues were observed. Results hAMSCs were found in the cortex and hippocampal areas of APP/PS1 and WT mice. hAMSCs transplantation significantly increased CD31 and Tie-2 expression in AD mice compared with the control group. Conclusions The study indicates that hAMSCs can cross the blood-brain barrier and enter the cerebral tissue of the mouse, transplantation of hAMSCs may promote angiogenesis in the AD model. The Ang-1/Tie-2 signaling pathway may be a therapeutically attractive target for the hAMSCs treatment of AD.