干细胞衍生物:突破活细胞治疗局限的多靶点脑细胞保护生物制品OA

For neurological deficits caused by nervous system diseases,the clinical efficacy of conventional single-target brain cytoprotective agents is limited.Although stem cell therapy holds the potential for multi-target brain cytoprotection,its clinical translation is hindered by challenges such as a low in vivo survival rate,potential to induce intracerebral inflammation,and risks of tumorigenicity.Stem cell derivatives are acellular biological products that,by enriching the paracrine active components(including stem cell secretome and extracellular vesicles),retain the pleiotropic brain cytoprotective functions of stem cells while significantly circumventing the safety and heterogeneity risks associated with live cell therapy.This article systematically reviews the mechanisms of action of stem cell derivatives and the current status of related basic and clinical research.Regarding the mechanisms of action,these derivatives can modulate the inflammatory and immune microenvironment,promote angiogenesis and neuroregeneration,and mediate intercellular substance transport,thereby establishing a new paradigm for systemic neural repair and regeneration in brain cytoprotection.Currently,stem cell derivatives have shown preliminary brain cytoprotective potential and favorable safety in research on diseases such as amyotrophic lateral sclerosis,multiple system atrophy,and ischemic stroke.Notably,in the context of increasingly stringent biomedical research and translational regulatory frameworks,as an"off-the-shelf"strategy with greater potential for standardization and industrialization,stem cell derivatives are expected to overcome the current druggability limitations in brain cytoprotection therapy and usher the field into an era of noncellular biological products.