Transplanted astrocytes derived from BMP- or CNTF-treated glial-restricted precursors have opposite effects on recovery and allodynia after spinal cord injury

Journal of Biology, 2008 · DOI: 10.1186/jbiol85 · Published: September 19, 2008

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study explores the effects of transplanting different types of astrocytes, derived from glial-restricted precursor cells (GRPs) treated with either bone morphogenetic protein-4 (BMP-4) or ciliary neurotrophic factor (CNTF), into rat spinal cord injuries. The research found that astrocytes derived from BMP-4 treated GRPs (GDAsBMP) promoted axon regeneration and functional recovery, while astrocytes derived from CNTF treated GRPs (GDAsCNTF) did not. Importantly, GDAsCNTF and undifferentiated GRPs caused neuropathic pain, whereas GDAsBMP did not, highlighting the importance of carefully evaluating cell types before clinical trials.

Study Duration

5 weeks

Participants

Adult female Sprague Dawley rats (3 months old)

Evidence Level

Not specified

Key Findings

1
GDAsBMP promote axon regeneration, neuroprotection and robust recovery of function after spinal cord injury, whereas GDAsCNTF do not.
2
Transplantation of GDAsCNTF or undifferentiated GRPs into spinal cord injuries resulted in mechanical allodynia and thermal hyperalgesia.
3
GDAsCNTF and GRPs promote sprouting of CGRP c-fibers after spinal cord injury, which correlates with the development of neuropathic pain.

Research Summary

This study investigates the effects of transplanting astrocytes derived from glial-restricted precursors (GRPs) treated with bone morphogenetic protein-4 (BMP-4) or ciliary neurotrophic factor (CNTF) into spinal cord injuries. The researchers found that GDAsBMP (astrocytes derived from BMP-4 treated GRPs) promoted axon regeneration, neuroprotection, and functional recovery, while GDAsCNTF (astrocytes derived from CNTF treated GRPs) did not. GDAsCNTF and undifferentiated GRPs induced mechanical allodynia and thermal hyperalgesia, whereas GDAsBMP did not, emphasizing the importance of careful cell selection in transplantation therapies.

Practical Implications

Cell Selection in Transplantation

Careful selection and pre-differentiation of cells are crucial for successful transplantation therapies for spinal cord injury, as different astrocyte subtypes have opposing effects.

Understanding Neuropathic Pain

Further research into the mechanisms by which GDAsCNTF and GRPs induce neuropathic pain could lead to novel therapeutic targets for treating pain after spinal cord injury.

Clinical Trial Design

Clinical trials involving cell transplantation for spinal cord injury must include thorough evaluations of potential adverse effects, such as allodynia, to ensure patient safety and efficacy.

Study Limitations

1
The study was conducted exclusively on rats, and the results may not be directly applicable to humans.
2
The mechanisms by which GDAsCNTF and GRPs induce allodynia were not fully elucidated.
3
The long-term effects of GDAsBMP transplantation were not evaluated beyond 5 weeks post-injury.

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