时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
With the steady rise in global life expectancy, neurodegenerative disorders (NDs) have emerged as one of the most pressing public health challenges of the 21st century.；To address this therapeutic gap, regenerative medicine has focused on stem cell-based therapies over the last few decades.
方法
Another major translational challenge is the limited mechanistic understanding of how cell-free therapeutics work, as it is hard to identify the important active components, set the right doses, predict how well the treatment will work, and meet the requirements for it to be approved.；Another significant challenge in the clinical translation of secretome and EVs is the lack of standardized and validated potency assays.；Therefore, to ensure that these secretome and EV formulations are equivalent for utilization in a clinical context, it is necessary to develop a range of potency assay strategies.
核心结论
In fact, it involves a highly interconnected network of dysregulated cellular pathways, ranging from chronic neuroinflammation and oxidative stress to mitochondrial dysfunction and protein misfolding, which current therapies fail to arrest or reverse (; ; ; ; ).；Consequently, the use of stem cell-derived products, either as a complex mixture (i.e., the secretome) or as isolated, targeted components (i.e., extracellular vesicles (EVs) and specific microRNAs), has gained significant attention as a strategy to restore physiological homeostasis, particularly in NDs.；Different factors can contribute to mitochondria dysfunction, such as elevated reactive oxygen species (ROS) levels, mtDNA mutations and impaired mitophagy, which ultimately results in reduced ATP production, imbalance in Ca2+ levels, and, eventually, apoptosis (; ; ; ; ). ‖ 结论：While this concept has relevance for neurodegenerative disorders, its implications are likely to extend across a broad range of chronic diseases characterized by disrupted intracellular homeostasis, opening new avenues for precision regenerative medicine.
局限
Beyond limiting oxidative damage, improved redox homeostasis preserves mitochondrial function, supports efficient protein folding within the ER, and facilitates autophagic degradation (; ; ; ).；To tackle this, further studies should focus on approaches capable of resolving organelle proximity and contact-site composition, such as in situ or electron microscopy, super-resolution imaging, genetically encoded membrane-contact-site reporters, FRET-based proximity sensors, or proximity-labeling proteomics targeting contact-site proteins.
对本项目的价值
★☆☆☆☆ 干细胞衰竭与部分重编程决定 rejuvenation 路线的可行边界与安全上限。
全文来源
PMC JATS 全文（正文 51,803 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Beyond cell replacement: restoring organelle homeostasis as the next frontier of regenerative medicine.
- 期刊与标识：Front Bioeng Biotechnol · PMID 42947811 · DOI 10.3389/fbioe.2026.1953752
B 级证据分级：B 级（同行评议临床前研究，主要为动物模型）
本文核心结论来自动物模型或体外细胞学，属临床前证据，不能外推至人体。「延长健康寿命」「改善功能」等表述在小鼠中的意义，与人类临床结局之间仍有距离。
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