Regeneration Of Sensory Fibers Research Articles

Combination of heterologous fibrin sealant and bioengineered human embryonic stem cells to improve regeneration following autogenous sciatic nerve grafting repair

BackgroundPeripheral nerve injury is a worldwide clinical problem, and the preferred surgical method for treating it is the end-to-end neurorrhaphy. When it is not possible due to a large nerve gap, autologous nerve grafting is used. However, these surgical techniques result in nerve regeneration at highly variable degrees. It is thus very important to seek complementary techniques to improve motor and sensory recovery. One promising approach could be cell therapy. Transplantation therapy with human embryonic stem cells (hESCs) is appealing because these cells are pluripotent and can differentiate into specialized cell types and have self-renewal ability. Therefore, the main objective of this study was to find conditions under which functional recovery is improved after sciatic nerve neurorrhaphy. We assumed that hESC, either alone or in combination with heterologous fibrin sealant scaffold, could be used to support regeneration in a mouse model of sciatic nerve injury and repair via autografting with end-to-end neurorrhaphy.MethodsFive millimeters of the sciatic nerve of C57BL/6 J mice were transected off and rotated 180 degrees to simulate an injury, and then stumps were sutured. Next, we applied heterologous fibrin sealant and/or human embryonic stem cells genetically altered to overexpress fibroblast growth factor 2 (FGF2) at the site of the injury. The study was designed to include six experimental groups comprising neurorrhaphy (N), neurorrhaphy + heterologous fibrin sealant (N + F), neurorrhaphy + heterologous fibrin sealant + doxycycline (N + F + D), neurorrhaphy + heterologous fibrin sealant + wild-type hESC (N + F + W), neurorrhaphy + heterologous fibrin sealant + hESC off (N + F + T), and neurorrhaphy + heterologous fibrin sealant + hESC on via doxycycline (N + F + D + T). We evaluated the recovery rate using Catwalk and von Frey functional recovery tests, as well as immunohistochemistry analysis.ResultsThe experiments indicated that sensory function improved when transgenic hESCs were used. The regeneration of sensory fibers indeed led to increased reflexes, upon stimulation of the paw ipsilateral to the lesion, as seen by von-Frey evaluation, which was supported by immunohistochemistry.ConclusionsOverall, the present data demonstrated that transgenic embryonic stem cells, engineered to overexpress FGF-2 in an inducible fashion, could be employed to support regeneration aiming at the recovery of both motor and sensory functions.

Comparison of Recovery of Tactile Function and Sensation after Median or Ulnar Nerve Lesions Repaired by Suture or Nerve Guide (P06.150)

Objective: The purpose of the study was to ascertain regeneration of sensory fibers and recovery of sensation after complete lesions of the median or ulnar nerve in the distal forearm and to compare repair carried out by direct suture or the use of a collagen nerve guide. Background After complete nerve lesions peripheral nerve fibers have the capacity to regenerate. Recovery is dependent of the rate of growth of fibers, the number of axons that regenerate, innervation of target tissue and maturation of regenerated fibers. Recovery is often incomplete, and patients usually are left with sensory and motor deficits. Design/Methods: In this randomized multi-center study two surgical procedures for repair of complete nerve lesions were compared. The collagen nerve guide (NeuraGen™) was implanted in 22 of 43 patients and direct suture repair was used in 20 patients and a short graft in 1 patient. The main outcome measures included clinical pain, sensory-motor- hand-function tests - RosenScore (J Hand Surg 2000;25A:535-43) and electrophysiological studies at 1 and 2 years after repair. In a subgroup consisting of 9 nerves repaired by nerve graft and in 9 by nerve guide, tactile function was studied by recording of sensory potentials using near-nerve needles. The stimulus was a fast indentation of 300 um applied to the tip of digit 3 or digit 5. Results: Tactile sensory potentials were recorded in all 18 patients with no difference in the amplitudes or areas after the two repair procedures. The amplitudes and areas were about 50% of those recorded from the contralateral normal hand. The findings were comparable to those obtained at hand function tests. Conclusions: Regeneration over short gap was supported as well by nerve guide as by suture and in the present patient group partial recovery of sensation and sensory fiber function was observed. Supported by: Integra LifeSciences Corp. Disclosure: Dr. Krarup has received personal compensation for activities with Integra LifeSciences as a speaker. Dr. Krarup has received research support from Integra LifeSciences and Shire. Dr. Rosen has nothing to disclose. Dr. Boeckstyns has nothing to disclose. Dr. Ibsen has nothing to disclose. Dr. Archibald has received personal compensation for activities with Integra LifeSciences Corp. as an employee.

Pretreatment of rats with pulsed electromagnetic fields enhances regeneration of the sciatic nerve.

Regeneration of the sciatic nerve was studied in rats pretreated in a pulsed electromagnetic field (PEMF). The rats were exposed between a pair of Helmholtz coils at a pulse repetition rate of 2 pps at a field density of 60 or 300 microT. The PEMF treatment was then discontinued. After an interval of recovery, regeneration of the sciatic nerve was initiated by a crush lesion. Regeneration of sensory fibers was measured by the "pinch test" after an additional 3-6 days. A variety of PEMF pretreatments including 4 h/day for 1-4 days or exposure for 15 min/day during 2 days resulted in an increased regeneration distance, measured 3 days after the crush lesion. This effect could be demonstrated even after a 14-day recovery period. In contrast, pretreatment for 4 h/day for 2 days at 60 microT did not affect the regeneration distance. The results showed that PEMF pretreatment conditioned the rat sciatic nerve in a manner similar to that which occurs after a crush lesion, which indicates that PEMF affects the neuronal cell body. However, the mechanism of this effect remains obscure.

Insulin-like growth factor I (IGF-I) stimulates regeneration of the rat sciatic nerve

The effect of insulin-like growth factor I (IGF-I) was tested on regeneration of the rat sciatic nerve after a crush lesion. IGF-I was administered via miniosmotic pumps to the dorsal root ganglia or locally around the crus lesion. Regeneration of sensory fibers was measured after 3 or 4 days superfusion by pinching. IGF-I stimulated regeneration in both administration paradigms. Regeneration was inhibited if the nerve was perfused with specific antibodies to native IGF-I. The results suggest that endogenous extracellular IGF-I plays an important role during regeneration of peripheral nerve fibers.