[Regeneration of the central nervous system using iPS cell-technologies]
1Department of Physiology, Keio University School of Medicine.
Rinsho Shinkeigaku = Clinical Neurology
|December 25, 2009
Summary
Induced pluripotent stem (iPS) cells offer a promising source for cell therapies. Careful evaluation of iPS-derived neural stem cells is crucial to prevent tumor formation and ensure safety for treating conditions like spinal cord injury.
Area of Science:
- Stem cell biology
- Regenerative medicine
- Neuroscience
Background:
- Induced pluripotent stem (iPS) cells are generated from somatic cells, avoiding ethical concerns and immune rejection associated with embryonic stem (ES) cells.
- iPS cells hold potential for cell replacement therapies, but their safety, particularly regarding tumorigenicity, needs thorough investigation.
- Neural stem/progenitor cells derived from iPSCs are being explored for therapeutic applications, including spinal cord injury (SCI).
Purpose of the Study:
- To investigate the tumorigenicity of neural stem/progenitor cells derived from various mouse iPSCs.
- To determine the factors influencing the tumorigenicity of iPS-derived neural stem cells.
- To evaluate the therapeutic potential of non-tumorigenic iPS-derived neural stem cells in a mouse spinal cord injury model.
Main Methods:
- Reprogramming mouse fibroblasts into iPS cells using Oct3/4, Sox2, c-Myc, and Klf4.
- Generating secondary neurospheres (SNSs) from iPS cells and assessing their neural differentiation capacity.
- Transplanting iPS-derived SNSs into the brains of immunodeficient NOD/SCID mice to evaluate teratoma formation.
- Generating iPSCs without c-Myc and drug selection, and evaluating their tumorigenicity.
- Transplanting non-tumorigenic Nanog-iPS-derived SNSs into a mouse spinal cord injury (SCI) model.
Main Results:
- Secondary neurospheres (SNSs) derived from various mouse iPSCs demonstrated neural differentiation capacity but also formed teratomas after transplantation.
- The origin of somatic cells used for iPS cell generation was a critical determinant of tumorigenicity in iPS-derived neural stem/progenitor cells.
- Tumorigenicity was linked to the persistent presence of undifferentiated cells within the SNSs.
- SNSs derived from c-Myc minus iPSCs, generated without drug selection, exhibited robust tumorigenesis despite contributing to chimeric mice without tumors.
- Transplantation of non-tumorigenic Nanog-iPS-derived SNSs promoted locomotor function recovery in a mouse SCI model.
Conclusions:
- The source of somatic cells significantly impacts the tumorigenicity of iPS-derived neural stem/progenitor cells.
- Persistent undifferentiated cells in iPS-derived neural stem/progenitor cell populations are responsible for tumorigenesis.
- Proper pre-evaluation of iPS cell clones is essential to ensure the safety and efficacy of neural stem/progenitor cells for transplantation therapies.
- iPS cell-derived neural stem/progenitor cells represent a promising, albeit carefully evaluated, cell source for treating spinal cord injury.
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Somatic cells are...
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