Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ILK-PI3K/AKT pathway

Chemotherapy can significantly reduce follicle counts in ovarian tissues and damage ovarian stroma,causing endocrine disorder,reproductive dysfunction,and primary ovarian insufficiency(POI).Recent studies have suggested that extracellular vesicles(EVs)secreted from mesenchymal stem cells(MSCs)exert therapeutic effects in various degenerative diseases.In this study,transplantation of EVs from human induced pluripotent stem cell-derived MSCs(iPSC-MSC-EVs)resulted in significant restoration of ovarian follicle numbers,improved granulosa cell proliferation,and inhibition of apoptosis in chemotherapy-damaged granulosa cells,cultured ovaries,and in vivo ovaries in mice.Mechanistically,treatment with i PSC-MSC-EVs resulted in up-regulation of the integrinlinked kinase(ILK)-PI3K/AKT pathway,which is suppressed during chemotherapy,most likely through the transfer of regulatory microRNAs(miRNAs)targeting ILK pathway genes.This work provides a framework for the development of advanced therapeutics to ameliorate ovarian damage and POI in female chemotherapy patients.

Microglia activation,classification and microglia-mediated neuroinflammatory modulators in subarachnoid hemorrhage

Subarachnoid hemorrhage is a devastating disease with significant mortality and morbidity,despite advances in treating cerebral aneurysms.There has been recent progress in the intensive care management and monitoring of patients with subarachnoid hemorrhage,but the results remain unsatisfactory.Microglia,the resident immune cells of the brain,are increasingly recognized as playing a significant role in neurological diseases,including subarachnoid hemorrhage.In early brain injury following subarachnoid hemorrhage,microglial activation and neuroinflammation have been implicated in the development of disease complications and recovery.To understand the disease processes following subarachnoid hemorrhage,it is important to focus on the modulators of microglial activation and the pro-inflammatory/anti-inflammatory cytokines and chemokines.In this review,we summarize research on the modulators of microglia-mediated inflammation in subarachnoid hemorrhage,including transcriptome changes and the neuroinflammatory signaling pathways.We also describe the latest developments in single-cell transcriptomics for microglia and summarize advances that have been made in the transcriptome-based classification of microglia and the implications for microglial activation and neuroinflammation.