Cell子刊：突破血脑屏障新思路，利用iPSC-小胶质细胞，治疗阿尔茨海默病等多种大脑疾病

Core Viewpoint - The article discusses the challenges and advancements in delivering therapeutic molecules across the blood-brain barrier (BBB), particularly focusing on the potential of using CRISPR-modified human induced pluripotent stem cell-derived microglia (iMG) for treating central nervous system (CNS) diseases [1][4][18]. Group 1: Blood-Brain Barrier and Its Implications - The blood-brain barrier is crucial for preventing harmful substances from entering the brain but also limits the delivery of most small and large molecule drugs, hindering the treatment of CNS diseases [1][2]. - There is an urgent need for technologies that can effectively deliver biotherapeutics across the BBB to improve treatment options for CNS disorders [2]. Group 2: Research Developments - A study published by researchers at the University of California, Irvine, demonstrated the use of CRISPR-modified iMG for CNS-wide delivery of disease-modifying proteins, showing potential in treating Alzheimer's disease, breast cancer brain metastasis, and demyelination [3][4][18]. - The research indicates that iMG can respond to pathological changes and deliver therapeutic proteins effectively, reducing various pathological biochemical markers associated with Alzheimer's disease [16][18]. Group 3: Delivery Mechanisms and Challenges - Previous attempts to deliver therapeutic antibodies using non-invasive techniques have shown limited success, with concentrations in the brain remaining below 2% of plasma levels [7]. - Direct injection methods for proteins or viral vectors have also faced challenges, including the need for multiple treatments for long-term efficacy and potential immune reactions [8][9]. Group 4: Future Prospects - iMG derived from human induced pluripotent stem cells present a promising new platform for cell therapy, capable of delivering therapeutic molecules across the CNS [10][12][16]. - The study's findings suggest that iMG can alleviate Aβ pathology and reduce inflammation and neurodegeneration, indicating a significant advancement in the treatment of CNS diseases [16][18].