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  4. Cell Transplantation for Spinal Cord Injury: Tumorigenicity of Induced Pluripotent Stem Cell-Derived Neural Stem/Progenitor Cells

Cell Transplantation for Spinal Cord Injury: Tumorigenicity of Induced Pluripotent Stem Cell-Derived Neural Stem/Progenitor Cells

Stem Cells International, 2018 · DOI: https://doi.org/10.1155/2018/5653787 · Published: February 4, 2018

Spinal Cord InjuryRegenerative Medicine

Simple Explanation

Spinal cord injury (SCI) presents a significant medical challenge with limited treatment options. While neural stem/progenitor cell (NS/PC) transplantation has shown promise, concerns about ethical issues and immune rejection exist. Induced pluripotent stem cells (iPSCs) offer a potential solution, but concerns about tumorigenicity are emerging. This review focuses on the tumorigenicity of iPSC-derived NS/PCs, discussing teratoma and true tumor formation. The review also explores the underlying mechanisms behind tumorigenicity and possible solutions to mitigate these risks, aiming to improve the safety of iPSC-based therapies for SCI.

Study Duration
Not specified
Participants
Not specified
Evidence Level
Review Article

Key Findings

  • 1
    Tumorigenicity of iPSCs can be classified into two types: teratomas, which arise from undifferentiated cells, and true tumors, which are often malignant and can metastasize.
  • 2
    Teratoma formation is largely attributed to the presence of residual undifferentiated iPSCs in the graft, while true tumors are associated with genomic and epigenomic instability.
  • 3
    Strategies to prevent teratoma formation include increasing the number of passages to weaken epigenetic memory, improving purification methods, and transplanting more mature cells.

Research Summary

This review discusses the application of iPSCs in SCI treatment, focusing on their tumorigenicity. It explains the two types of tumorigenicity: teratoma formation and substantial tumor formation, highlighting the underlying mechanisms. The review suggests potential solutions to mitigate the risk of tumorigenesis, including improving purification methods, using integration-free reprogramming methods, and avoiding transgenic factors of oncogenesis. Despite the challenges, the review recognizes the potential of iPSCs for SCI treatment due to their self-renewal and differentiation abilities. More research is needed to fully understand and address the safety concerns.

Practical Implications

Improved safety protocols

Development of robust protocols to ensure complete differentiation of iPSCs before transplantation can reduce the risk of teratoma formation.

Optimized reprogramming methods

Adopting integration-free reprogramming methods and avoiding oncogenic factors during iPSC generation can minimize the risk of true tumor formation.

Enhanced clone selection

Establishing reliable methods to distinguish safe and unsafe cell clones can facilitate the selection of non-tumorigenic iPSC-derived cells for transplantation.

Study Limitations

  • 1
    Incomplete understanding of tumorigenesis mechanisms
  • 2
    Challenges in translating in vitro strategies to clinical applications
  • 3
    Lack of long-term safety data for iPSC-based therapies

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