Abstract

Mesenchymal stem cells (MSCs) hold a great promise for cell therapy. To date, they represent one of the best choices for the treatment of post-traumatic injuries of the peripheral nervous system. Although autologous can be easily transplanted in the injured area, clinical advances in this filed have been impaired by lack of preservation of graft cells into the injury area after transplantation. Indeed, cell viability is not retained after injection into the blood stream, and cells injected directly into the area of injury either are washed off or inhibit regeneration through scar formation and neuroma development. This study proposes a new way of MSCs delivery to the area of traumatic injury by using fibrin glue, which not only fixes cells at the site of application but also provides extracellular matrix support. Using a sciatic nerve injury model, MSC derived from adipose tissue embedded in fibrin glue were able to enter the nerve and migrate mainly retrogradely after transplantation. They also demonstrated a neuroprotective effect on DRG L5 sensory neurons and stimulated axon growth and myelination. Post-traumatic changes of the sensory neuron phenotype were also improved. Importantly, MSCs stimulated nerve angiogenesis and motor function recovery. Therefore, our data suggest that MSC therapy using fibrin glue is a safe and efficient method of cell transplantation in cases of sciatic nerve injury, and that this method of delivery of regeneration stimulants could be beneficial for the successful treatment of other central and peripheral nervous system conditions.

Highlights

  • Peripheral neuropathy caused by trauma and prevalent disorders is a major medical problem worldwide

  • We show that transplantation of Mesenchymal stem cells (MSCs) embedded in fibrin glue promotes regeneration through a neuroprotective effect on sensory neurons and stimulation of axon growth

  • Fluorescent green cells were detected 48 h after transduction and a population of adipose derived stem cells (ADSCs) expressing ≥90% eGFP was obtained after sorting (Figure 2) Transplantation of fluorescent sorted cells allowed the visualization of MSC integration in the injured area

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Summary

Introduction

Peripheral neuropathy caused by trauma and prevalent disorders is a major medical problem worldwide. Due to anatomy of the peripheral nervous system, structure damage of peripheral nerve trunks is a rather common condition. Nerve trunk injury is not a life-threatening condition, it is accompanied by a persistent complex of nociceptive, sensory, and motor as well as trophic changes that can result in long-lasting disability, with full recovery of lost extremity functions being difficult [1, 2]. When facilitating nerve structure recovery to reduce nerve tissue injury, the main focus is to use various organic glues that join the ends of the damaged nerve [9] or are part of nerve conduit [10]. Fibrin glue can induce faster re-innervation and function recovery due to reduced amount of scar tissue and directed axon growth [14, 15]

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