Spellicy Samantha E, Hess David C
MD-Ph.D. Program, Medical College of Georgia at Augusta University, Augusta, GA, United States.
Dean's Office, Medical College of Georgia at Augusta University, Augusta, GA, United States.
Front Cell Dev Biol. 2021 Mar 16;9:647415. doi: 10.3389/fcell.2021.647415. eCollection 2021.
Inflammation has proven to be a key contributing factor to the pathogenesis of ischemic and hemorrhagic stroke. This sequential and progressive response, marked by proliferation of resident immune cells and recruitment of peripheral immune populations, results in increased oxidative stress, and neuronal cell death. Therapeutics aimed at quelling various stages of this post-stroke inflammatory response have shown promise recently, one of which being differentiated induced pluripotent stem cells (iPSCs). While direct repopulation of damaged tissues and enhanced neurogenesis are hypothesized to encompass some of the therapeutic potential of iPSCs, recent evidence has demonstrated a substantial paracrine effect on neuroinflammation. Specifically, investigation of iPSCs, iPSC-neural progenitor cells (iPSC-NPCs), and iPSC-neuroepithelial like stem cells (iPSC-lt-NESC) has demonstrated significant immunomodulation of proinflammatory signaling and endogenous inflammatory cell populations, such as microglia. This review aims to examine the mechanisms by which iPSCs mediate neuroinflammation in the post-stroke environment, as well as delineate avenues for further investigation.
炎症已被证明是缺血性和出血性中风发病机制的关键促成因素。这种以驻留免疫细胞增殖和外周免疫群体募集为特征的连续渐进性反应，会导致氧化应激增加和神经元细胞死亡。旨在平息中风后炎症反应各个阶段的治疗方法最近已显示出前景，其中之一是分化诱导多能干细胞（iPSC）。虽然推测受损组织的直接再填充和增强的神经发生涵盖了iPSC的一些治疗潜力，但最近的证据表明其对神经炎症有显著的旁分泌作用。具体而言，对iPSC、iPSC神经祖细胞（iPSC-NPC）和iPSC神经上皮样干细胞（iPSC-lt-NESC）的研究表明，它们对促炎信号传导和内源性炎症细胞群体（如小胶质细胞）具有显著的免疫调节作用。本综述旨在探讨iPSC在中风后环境中介导神经炎症的机制，并描绘进一步研究的途径。
