Inhibiting Cell Inspection Points Intervention via Injectable Short Fibers for Reversing Neural Cell Senescence

Neurology Biochemistry Life Sciences Cell Biology Bioengineering Medicine Neurosurgery
neural cell senescence inspection point short fibers spinal cord genome homeostasis

Background Introduction

Spinal Cord Injury (SCI) is a significant challenge in the medical field, particularly in terms of neural function recovery. Research indicates that neurons play a crucial role in spinal cord regeneration, but in complex pathological environments, neurons are influenced by various factors, leading to rapid senescence. Senescent neural cells not only lose their proliferative capacity but also induce surrounding cells into a senescent state through the secretion of Senescence-Associated Secretory Phenotype (SASP), creating a vicious cycle that exacerbates local tissue degeneration. Current treatments, such as senolytic therapies that clear senescent cells, provide short-term symptom relief but fail to address the root cause of cellular senescence. Therefore, discovering novel therapeutic approaches to reverse neural cell senescence and promote neural function recovery has become a research priority.

Source of the Paper

This research was collaboratively conducted by a team from Shanghai Jiao Tong University School of Medicine, Wenzhou Institute, University of Chinese Academy of Sciences, and other institutions. The primary authors include Qianyi Li, Liang Chen, Jie Yu, and others. The paper was published on January 9, 2025, in the journal Advanced Fiber Materials, titled “Inhibiting Cell Inspection Points Intervention via Injectable Short Fibers for Reversing Neural Cell Senescence”.

Research Process and Results

1. Research Design and Experimental Process

The core objective of this study was to develop an injectable short fiber system that reverses neural cell senescence by inhibiting excessive cell inspection point intervention, thereby promoting spinal cord neural function recovery. The research was divided into the following main steps:

1.1 Preparation of Oxidation-Sensitive Liposomes

First, the research team prepared oxidation-sensitive liposomes (n-Bak), whose core component is Bakuchiol (Bak), a natural plant extract with DNA-protective properties. The liposomes, combined with thioether phospholipids (S-PC), can release Bak in response to excessive Reactive Oxygen Species (ROS), thereby protecting DNA from damage.

1.2 Construction of Functional Short Fibers

Next, the research team combined oxidation-sensitive liposomes with short fibers through π-π conjugation and Polydopamine (PDA) modification to construct functional short fibers (ISN@n-Bak). These fibers not only respond to ROS in the damaged microenvironment to release Bak but also provide structural support for neural cell growth and differentiation through their three-dimensional architecture.

1.3 In Vitro Experimental Validation

In in vitro experiments, the research team co-cultured ISN@n-Bak with mouse neural stem cells to observe its promotion of neuronal differentiation. The results showed that ISN@n-Bak significantly promoted the differentiation of neural stem cells into neurons and exhibited anti-aging effects in cells at different senescence stages.

1.4 In Vivo Experimental Validation

In in vivo experiments, the research team injected ISN@n-Bak into the spinal cord injury sites of mice and evaluated its impact on neural function recovery through behavioral, morphological, and immunohistochemical analyses. The results demonstrated that ISN@n-Bak significantly improved motor function in mice, reduced cavity formation in the injured spinal cord area, and promoted neural cell regeneration.

2. Key Research Findings

2.1 In Vitro Experimental Results

ISN@n-Bak exhibited significant anti-aging and neural regeneration-promoting capabilities in in vitro experiments. Through β-galactosidase (SA-β-gal) staining, Edu, and TUNEL fluorescence staining, the research team found that ISN@n-Bak significantly reduced the proportion of senescent cells, promoted cell proliferation, and decreased cell apoptosis.

2.2 In Vivo Experimental Results

In the mouse model of spinal cord injury, ISN@n-Bak significantly improved motor function, reduced cavity formation in the injured spinal cord area, and promoted neural cell regeneration. Immunofluorescence staining further revealed that ISN@n-Bak decreased the expression of the DNA damage marker γ-H2AX, indicating its notable efficacy in protecting DNA integrity.

2.3 Transcriptomic and Single-Cell Sequencing Analysis

Through whole transcriptome sequencing and single-cell sequencing, the research team further elucidated the mechanisms of ISN@n-Bak. The results showed that ISN@n-Bak downregulated senescence-related genes (such as CDKN2A and CDKN2C), inhibited the PI3K-AKT signaling pathway, and upregulated the RAP1 pathway, which promotes neural regeneration.

3. Conclusion and Significance

This study is the first to develop an injectable short fiber system that reverses neural cell senescence by inhibiting cell inspection point intervention. The system not only responds to ROS in the damaged microenvironment to release Bak and protect DNA integrity but also provides structural support for neural cell growth and differentiation. Through whole transcriptome and single-cell sequencing, the research team further clarified the mechanisms of ISN@n-Bak, providing a theoretical foundation for its application in spinal cord injury treatment.

4. Research Highlights

  • Innovative Therapeutic Strategy: This study is the first to combine oxidation-sensitive liposomes with short fibers, proposing a novel method to reverse neural cell senescence by inhibiting cell inspection point intervention.
  • Multiple Mechanisms of Action: ISN@n-Bak not only protects DNA from damage but also promotes neural cell growth and differentiation through its three-dimensional structure.
  • Comprehensive Research: Through in vitro and in vivo experiments, as well as transcriptomic and single-cell sequencing, the research team thoroughly elucidated the mechanisms of ISN@n-Bak, providing a solid theoretical basis for its clinical application.

Summary

This study offers a novel approach to spinal cord injury treatment by reversing neural cell senescence through the inhibition of cell inspection point intervention, potentially bringing new hope to patients with spinal cord injuries. In the future, the research team will further optimize this system to advance its clinical application.