Efficacy of Schwann cell transplantation for spinal cord repair is improved with combinatorial strategies

Mary B Bunge

Research output: Contribution to journalReview article

25 Citations (Scopus)

Abstract

When cells (including Schwann cells; SCs) of the peripheral nervous system (PNS) could be purified and expanded in number in tissue culture, Richard Bunge in 1975 envisioned that the SCs could be introduced to repair the central nervous system (CNS), as SCs enable axons to regenerate after PNS injury. Importantly, autologous human SCs could be transplanted into injured human spinal cord. Availability of the new culture systems to study interactions between sensory neurons, SCs and fibroblasts increased our knowledge of SC biology in the 1970s and ’80s. Joining the Miami Project to Cure Paralysis in 1989 brought the opportunity to use this knowledge to initiate spinal cord repair studies. Development of a rat complete spinal cord transection/SC bridge model allowed the demonstration that axons regenerate into the SC bridge. Together with study of contused rat spinal cord, it was concluded that implanted SCs reduce cavitation, protect tissue around the lesion, support axon regeneration and form myelin. SC transplantation efficacy was improved when combined with neurotrophins, elevation of cyclic AMP levels, olfactory ensheathing cells, a steroid or chondroitinase. Increased efficacy meant higher numbers of axons, particularly from the brainstem, and more SC-myelinated axons in the implants and improvement in hindlimb movements. Human SCs support axon regeneration as do rat SCs. Astrocytes at the SC bridge–host spinal cord interfaces play a key role in determining whether axons enter the SC milieu. The SC work described here contributed to gaining approval from the FDA for an initial autologous human SC clinical trial (at the Miami Project) that has been completed and found to be safe. (Figure presented.) .

Original languageEnglish (US)
Pages (from-to)3533-3538
Number of pages6
JournalJournal of Physiology
Volume594
Issue number13
DOIs
StatePublished - Jul 1 2016

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Spinal Cord Regeneration
Schwann Cells
Cell Transplantation
Axons
Spinal Cord
Peripheral Nervous System
Regeneration
Chondroitinases and Chondroitin Lyases
Nervous System Trauma
Contusions
Nerve Growth Factors
Sensory Receptor Cells
Hindlimb
Myelin Sheath
Spinal Cord Injuries
Astrocytes
Paralysis
Cyclic AMP
Brain Stem
Central Nervous System

ASJC Scopus subject areas

  • Physiology

Cite this

Efficacy of Schwann cell transplantation for spinal cord repair is improved with combinatorial strategies. / Bunge, Mary B.

In: Journal of Physiology, Vol. 594, No. 13, 01.07.2016, p. 3533-3538.

Research output: Contribution to journalReview article

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