論文紹介著者

WU HAO（博士課程 1年）
GCOE　RA
整形外科 (Department of Orthopedic Surgery)

第一著者名・掲載雑誌・号・掲載年月

NARIHITO NAGOSHI／NARIHITO NAGOSHI,^1,2,3 SHINSUKE SHIBATA,¹ MAKOTO HAMANOUE,⁴ YO MABUCHI,¹ YUMI MATSUZAKI,¹. GLIA 59:771-784 (2011)

論文解説

Introduction

Only a few treatments are currently available for spinal cord injury (SCI), a life-threatening traumatic disorder, and full functional recovery is rare. The nervous tissue damage from SCI occurs in several stages, including a primary phase of physiological damage with hemorrhage or ischemia, and a secondary phase of further destruction by infiltrating inflammatory cells. During the secondary phase, various cell types are recruited to the site of injury and contribute to not only the degenerative response, but also the regenerative one.

Schwann cells, which normally inhabit the peripheral nerves, including the nerve roots, but not the intact spinal cord, appear in the spinal-cord lesion site and remyelinate (myelinate the injured myelin sheath again) the surviving axons.

Summary

After spinal cord injury (SCI), various cell types are recruited to the lesion site, including Schwann cells, which originate in　the neural crest and normally myelinate axons in the peripheral　nervous system. Authors investigated the differentiation states, migration patterns, and roles of neural crest derivatives following SCI, using two transgenic mouse lines carrying neural crest-specific fluorescence reporters(EGFP: Enhanced Green Fluorescent Protein). In these mice, EGFP is expressed only in the neural crest cell lineage. Most of the EGFP⁺ cells that infiltrated the lesion site after SCI were Schwann cells.

Seven days after SCI, the P0^-positive, mature Schwann cells residing at the nerve roots had dedifferentiated into P0^-/p75⁺ immature Schwann cells, which proliferated and began migrating into the lesion site.

Thereafter, the number of EGFP⁺/p75⁺ immature Schwann cells decreased and that of EGFP⁺/P0⁺ mature cells increased gradually, indicating that the cells redifferentiated into mature Schwann cells within the lesion site.

Conclusion

1. EGFP⁺ neural crest-derived cells migrate into the lesion epicenter from the peripheral nerves after SCI.
2. Mature Schwann cells of nerve roots dedifferentiate and migrate into the lesion site after SCI.
3. Immature Schwann cells reacquire their maturity and remyelinate axons at the lesion site.

Schwann cell migration into the CNS lesion site is a natural repair mechanism for SCI. Transplanted Schwann cells provide trophic support for spared axons and participate in their remyelination; furthermore, the recruitment of Schwann cells to the lesion site enhances functional recovery after SCI. Myelination contributes to functional recovery, the targeting of immature Schwann cells to enhance their redifferentiation could be a potential therapeutic strategy for SCI.

用語解説

• ※1　Spinal cord injury (SCI)：
  Spinal cord injury (SCI) refers to any injury to the spinal cord that is caused by trauma instead of disease. Depending on where the spinal cord and nerve roots are damaged, the symptoms can vary widely, from pain to paralysis to incontinence. Spinal cord injuries are described at various levels of "incomplete", which can vary from having no effect on the patient to a "complete" injury which means a total loss of function.
• ※2　P0：
  a marker for mature myelinating Schwann cells.
• ※3　p75：
  a marker of immature and nonmyelinating Schwann cells.