Transplantation of Embryonic Spinal Cord Derived Cells Helps to Prevent Muscle Atrophy after Peripheral Nerve Injury.

Carolin Ruven,Wai-Man Wong,Wutian Wu,Heng Li,Wen Li

doi:10.3390/ijms18030511

Abstract

Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat embryonic spinal cord fetal cells and cultured neural progenitor cells from different spinal cord segments were injected into transected musculocutaneous nerve of 200–300 g female Sprague Dawley (SD) rats, and atrophy in biceps brachii was assessed. Both kinds of cells were able to survive, extend their axons towards the muscle and form neuromuscular junctions that were functional in electromyographic studies. As a result, muscle endplates were preserved and atrophy was reduced. Furthermore, we observed that the fetal cells had a better effect in reducing the muscle atrophy compared to the pure neural progenitor cells, whereas lumbar cells were more beneficial compared to thoracic and cervical cells. In addition, fetal lumbar cells were used to supplement six weeks delayed surgical repair after the nerve transection. Cell transplantation helped to preserve the muscle endplates, which in turn lead to earlier functional recovery seen in behavioral test and electromyography. In conclusion, we were able to show that embryonic spinal cord derived cells, especially the lumbar fetal cells, are beneficial in the treatment of peripheral nerve injuries due to their ability to prevent the muscle atrophy.

Highlights

Peripheral nerve injuries occur frequently and affect 2.8% of trauma patients annually, resulting in loss of motor and sensory functions [1]
Our aim was to compare this kind of fetal cells with pure neural progenitor cells (NPCs) for their ability to survive in injured nerve and their ability to reinnervate the muscle and reduce the muscle atrophy
Very little work has been done in the field of using induced pluripotent stem cells (iPSCs) for nerve regeneration even though iPSCs would be more obtained from the same individual [67,68] compared to the NPCs that could be obtained only in small amounts from the adult spinal cord or from electively terminated human embryos [69]

Summary

Introduction

Peripheral nerve injuries occur frequently and affect 2.8% of trauma patients annually, resulting in loss of motor and sensory functions [1]. When the distance from the injury site to the target muscle is too long, for instance, following brachial plexus injury, the axonal regeneration at 1 mm/day [2,4] would take more than a year after injuries of nerves innervating muscles in the lower limbs. During this time, muscles lose the connection with axons, leading to degeneration of muscle endplates and severe muscle atrophy [5]. There is no effective treatment for clinical use to mitigate the muscle atrophy after peripheral nerve injuries

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