Human Placenta Derived Mesenchymal Stem Cells Transplantation Reducing Cellular Apoptosis in Hypoxic-Ischemic Neonatal Rats by Down-Regulating Semaphorin 3A/Neuropilin-1

hypoxic-ischemic encephalopathy (HIE) is an abnormal neurological condition caused by hypoxic-ischemic damage during the perinatal period. Human placenta derived mesenchymal stem cells (hPMSCs) have been shown to have protective and reparative effects in various neurological diseases; however, the research on HIE is insufficient. This study aimed to establish a rat model of HIE and transplant hPMSCs through the lateral ventricle after hypoxic-ishcemic (HI) brain damage to observe its protective effects and mech-anisms, with a focus on brain apoptosis compared among groups. Differentially expressed apoptosis-related pro-teins were screened using a rat cytokine array and subsequent verification. Neuropilin-1 (NRP-1) and Semaphorin 3A (Sema 3A) were selected for further investigation. Western blotting was used to quantify the expression of Sema 3A and the proteins related to PI3K/Akt/mTOR signaling pathway. Exogenous Sema 3A was added to eval-uate the effects of Sema 3A/NRP-1 on hPMSCs following HI injury. hPMSCs transplantation ameliorated HI-induced pathological changes, reduced apoptosis, and improved long-term neurological prognosis. Furthermore, Sema 3A/NRP-1 was a key regulator in reducing HI-induced apoptosis after hPMSCs transplantation. hPMSCs inhibited the expression of Sema 3A/NRP-1 and activated the PI3K/Akt/mTOR signaling pathway. Additionally, exogenous Sema 3A abolished the protective effects of hPMSCs against HI. In conclusion, hPMSCs transplanta-tion reduced apoptosis and improved long-term neurological prognosis after HI by downregulating Sema 3A/ NRP-1 expression and activating the PI3K/Akt/mTOR signaling pathway.(c) 2023 The Authors. Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.