Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China.
Center for Precision Medicine, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China.
Stem Cell Res Ther. 2024 Oct 29;15(1):383. doi: 10.1186/s13287-024-03986-9.
The prevalence of age-related disorders, particularly in neurological and cardiovascular systems, is an increasing global health concern. Mesenchymal stem cell (MSC) therapy, particularly using human umbilical cord-derived MSCs (HUCMSCs), has shown promise in mitigating these disorders. This study investigates the effects of HUCMSCs on aging-related conditions in a senescence-accelerated mouse model (SAMP8), with a focus on DNA damage, gut microbiota alterations, and metabolic changes.
SAMP8 mice were treated with clinical-grade HUCMSCs via intraperitoneal injections. Behavioral and physical assessments were conducted to evaluate cognitive and motor functions. The Single-Strand Break Mapping at Nucleotide Genome Level (SSiNGLe) method was employed to assess DNA single-strand breaks (SSBs) across the genome, with particular attention to exonic regions and transcription start sites. Gut microbiota composition was analyzed using 16S rRNA sequencing, and carboxyl metabolomic profiling was performed to identify changes in circulating metabolites.
HUCMSC treatment significantly improved motor coordination and reduced anxiety in SAMP8 mice. SSiNGLe analysis revealed a notable reduction in DNA SSBs in MSC-treated mice, especially in critical genomic regions, suggesting that HUCMSCs may mitigate age-related DNA damage. The functional annotation of the DNA breaktome indicated a potential link between reduced DNA damage and altered metabolic pathways. Additionally, beneficial alterations in gut microbiota were observed, including an increase in short-chain fatty acid (SCFA)-producing bacteria, which correlated with improved metabolic profiles.
The administration of HUCMSCs in SAMP8 mice not only reduces DNA damage but also induces favorable changes in gut microbiota and metabolism. The observed alterations in DNA break patterns, along with specific changes in microbiota and metabolic profiles, suggest that these could serve as potential biomarkers for evaluating the efficacy of HUCMSCs in treating age-related disorders. This highlights a promising avenue for the development of new therapeutic strategies that leverage these biomarkers, to enhance the effectiveness of HUCMSC-based treatments for aging-associated diseases.
与年龄相关的疾病（尤其是在神经和心血管系统中）的流行是一个日益严重的全球健康问题。间充质干细胞（MSC）治疗，特别是使用人脐带衍生的 MSC（HUCMSCs），已显示出在减轻这些疾病方面的潜力。本研究使用衰老加速模型（SAMP8）小鼠来研究 HUCMSC 对与年龄相关的疾病的影响，重点关注 DNA 损伤、肠道微生物群改变和代谢变化。
通过腹腔内注射向 SAMP8 小鼠施用临床级 HUCMSC。进行行为和身体评估，以评估认知和运动功能。使用核苷酸基因组水平的单链断裂作图（SSiNGLe）方法评估整个基因组的 DNA 单链断裂（SSBs），特别关注外显子区域和转录起始位点。使用 16S rRNA 测序分析肠道微生物群组成，并进行羧基代谢组学分析以鉴定循环代谢物的变化。
HUCMSC 治疗可显著改善 SAMP8 小鼠的运动协调能力并减轻焦虑。SSiNGLe 分析显示，MSC 治疗的小鼠的 DNA SSB 明显减少，特别是在关键基因组区域，这表明 HUCMSCs 可能减轻与年龄相关的 DNA 损伤。DNA 断裂组的功能注释表明，减少的 DNA 损伤与改变的代谢途径之间存在潜在联系。此外，还观察到肠道微生物群的有益改变，包括产生短链脂肪酸（SCFA）的细菌增加，这与改善的代谢谱相关。
在 SAMP8 小鼠中施用 HUCMSC 不仅减少了 DNA 损伤，而且还诱导了肠道微生物群和代谢的有益变化。观察到的 DNA 断裂模式的改变，以及微生物群和代谢谱的特定变化，表明这些可以作为评估 HUCMSC 治疗与年龄相关疾病疗效的潜在生物标志物。这突出了利用这些生物标志物开发新的治疗策略的有前途的途径，以增强基于 HUCMSC 的治疗方法对与衰老相关疾病的有效性。
