Epigenetic regulation and factors that influence the effect of iPSCs‑derived neural stem/progenitor cells (NS/PCs) in the treatment of spinal cord injury

Clinical Epigenetics, 2024 · DOI: https://doi.org/10.1186/s13148-024-01639-5 · Published: March 1, 2024

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

Spinal cord injury (SCI) is a severe neurological disorder that causes neurological impairment and disability. Neural stem/progenitor cells (NS/PCs) derived from induced pluripotent stem cells (iPSCs) represent a promising cell therapy strategy for spinal cord regeneration and repair. Epigenetics refers to the regulation of gene expression and function by DNA methylation, histone modification, and chromatin structure without changing the DNA sequence. Previous research has shown that epigenetics plays a crucial role in the generation, differentiation, and transplantation of iPSCs, and can influence the quality, safety, and outcome of transplanted cells. In this study, we review the effects of epigenetic regulation and various influencing factors on the role of iPSC-derived NS/PCs in SCI therapy at multiple levels, including epigenetic reprogramming, regulation, and the adaptation of iPSCs during generation, differentiation, and transplantation, as well as the impact of other therapeutic tools (e.g., drugs, electrical stimulation, and scaffolds) on the epigenetic status of transplanted cells.

Study Duration

From the 1st of January 2000 to the 31st of March 2023

Participants

Not specified

Evidence Level

Review article

Key Findings

1
Epigenetic reprogramming is a crucial step for generating iPSCs from somatic cells, as this process can determine their quality, safety and pluripotency. However, epigenetic reprogramming is often incomplete or inefficient, thus leading to residual epigenetic memory or aberrant epigenetic marks in iPSCs.
2
The epigenetic regulation of iPSCs during their differentiation into NS/PCs is influenced by various differentiation factors and culture conditions, which can influence the methylation, histone modification and chromatin structure of iPSCs and their differentiation.
3
Following transplantation into SCI patients or animal models, iPSC-derived NS/PCs face a different neural tissue environment in vivo than in in vitro culture conditions. This may lead to adaptive changes in the transplanted cells at the epigenetic level, which regulate their differentiation, migration, survival and interaction with host tissues

Research Summary

This article reviews how epigenetic regulation and various factors can influence iPSC-derived NS/PCs during SCI therapy at the molecular and functional levels. It describes how the epigenetic reprogramming, regulation and adaptation of iPSCs during their generation, differentiation and transplantation can influence the differentiation, migration, survival and interaction of transplanted cells with neural tissue in the host, thus influencing the efficacy and safety of SCI therapy. The review also describes how other therapies (e.g., drugs, electrical stimulation, and scaffolds) can modulate and synergize with the epigenetic status of transplanted cells to enhance the efficiency and efficacy of neurological recovery. The authors propose that the modification of iPSCs to render them more suitable for cell therapy is a promising direction for future research and development.

Practical Implications

Improve iPSC Generation

Optimize methods to generate iPSCs, reducing epigenetic differences between iPSCs and ESCs to enhance efficacy and safety in SCI therapy.

Optimize Differentiation Protocols

Refine differentiation factors and culture conditions to improve the quality and efficiency of iPSC-derived NS/PCs for SCI treatment, focusing on methylation, histone modification, and chromatin structure.

Enhance Post-Transplantation Adaptation

Understand and modulate epigenetic adaptations of iPSC-derived NS/PCs after transplantation to improve their differentiation, migration, survival, and interaction with host tissues, thereby enhancing neurological recovery.

Study Limitations

1
Limited studies on epigenetic adaptations of iPSC-derived NS/PCs in human models following transplantation.
2
Lack of systematic studies on the specific mechanisms and optimal combinations of co-treatments.
3
Current epigenetic detection methods in vivo after transplantation need improvement for simplicity, speed, precision and sensitivity.

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