Assessment of Axonal Growth into Collagen Nerve Guides Containing VEGF‐Transfected Stem Cells in Matrigel

Kempton, Laurence B.; Gonzalez, Mark H.; Leven, Robert M.; Hughes, William F.; Beddow, Sara A.; Santhiraj, Yaveen; Archibald, Simon J.; Hassan, Bassem El; Shott, Susan; Kerns, James M.

doi:10.1002/ar.20844

Cited by 14 publications

(14 citation statements)

References 57 publications

(93 reference statements)

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“…It has been demonstrated in various models of nerve injury that VEGF promotes axonal outgrowth and proliferation of Schwann cells to enhance nerve reinnervation [17,19,27]. In our experimental models of ETE and ETS neurorrhaphy, we found that plasmid phVEGF transfection of the MCN stumps resulted in an elevation of VEGF protein in Schwann cells.…”

Section: Discussionsupporting

confidence: 50%

Enhancement of musculocutaneous nerve reinnervation after vascular endothelial growth factor (VEGF) gene therapy

et al. 2012

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BackgroundVascular endothelial growth factor (VEGF) is not only a potent angiogenic factor but it also promotes axonal outgrowth and proliferation of Schwann cells. The aim of the present study was to quantitatively assess reinnervation of musculocutaneous nerve (MCN) stumps using motor and primary sensory neurons after plasmid phVEGF transfection and end-to-end (ETE) or end-to-side (ETS) neurorrhaphy. The distal stump of rat transected MCN, was transfected with plasmid phVEGF, plasmid alone or treated with vehiculum and reinnervated following ETE or ETS neurorrhaphy for 2 months. The number of motor and dorsal root ganglia neurons reinnervating the MCN stump was estimated following their retrograde labeling with Fluoro-Ruby and Fluoro-Emerald. Reinnervation of the MCN stumps was assessed based on density, diameter and myelin sheath thickness of regenerated axons, grooming test and the wet weight index of the biceps brachii muscles.ResultsImmunohistochemical detection under the same conditions revealed increased VEGF in the Schwann cells of the MCN stumps transfected with the plasmid phVEGF, as opposed to control stumps transfected with only the plasmid or treated with vehiculum. The MCN stumps transfected with the plasmid phVEGF were reinnervated by moderately higher numbers of motor and sensory neurons after ETE neurorrhaphy compared with control stumps. However, morphometric quality of myelinated axons, grooming test and the wet weight index were significantly better in the MCN plasmid phVEGF transfected stumps. The ETS neurorrhaphy of the MCN plasmid phVEGF transfected stumps in comparison with control stumps resulted in significant elevation of motor and sensory neurons that reinnervated the MCN. Especially noteworthy was the increased numbers of neurons that sent out collateral sprouts into the MCN stumps. Similarly to ETE neurorrhaphy, phVEGF transfection resulted in significantly higher morphometric quality of myelinated axons, behavioral test and the wet weight index of the biceps brachii muscles.ConclusionOur results showed that plasmid phVEGF transfection of MCN stumps could induce an increase in VEGF protein in Schwann cells, which resulted in higher quality axon reinnervation after both ETE and ETS neurorrhaphy. This was also associated with a better wet weight biceps brachii muscle index and functional tests than in control rats.

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Section: Discussionsupporting

confidence: 50%

Enhancement of musculocutaneous nerve reinnervation after vascular endothelial growth factor (VEGF) gene therapy

et al. 2012

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“…During peripheral nerve regeneration, TGF-β1 up-regulates beta fibroblast growth factor expression in the anterior horn motoneurons of the spinal cord [31]. VEGF administration has also been shown to support and enhance the growth of regenerating nerve fibers, probably through a combination of endogenous, neurotrophic and Neuroprotective effects [32][33][34]. SFI is a simple and repeatable method for evaluating the functional condition of sciatic nerve injuries.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Chick Embryo Cerebro-Spinal Fluid in Microwave Irradiated Collagen Guide Channel on Sciatic Nerve Regeneration in Rat

Ghavami

Dolatkhah

Farjah

2016

MOJAP

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The aim of this research was to evaluate the effect of chick embryo cerebrospinal fluid (e-CSF) across the irradiated collagen guide channel on sciatic nerve regeneration in comparison with autograft. Forty adult male Sprague-Dawley rats (250-300g) were randomized into (1) collagen channel + E-CSF, (2) collagen channel + normal saline (NS), (3) autograft (AG), and (4) sham surgery groups. The left sciatic nerve was exposed and a 10mm nerve segment was cut and removed. In the collagen groups, the proximal and distal cuts ends of sciatic nerve were telescoped into the nerve guides and E-CSF or NS injected into collagen conduit. To the autograft group, the 10 mm nerve segment was turned backwards and used an autologous nerve graft. All animals were evaluated by sciatic functional index (SFI) and electrophysiology testing. The improvements in SFI since the beginning of the last evaluation in experimental groups were measured. On days 49 and 60 post-operation, the mean SFI of the collagen + E-CSF group was significantly greater than the autograft group (P< 0.05). On day 90, the mean nerve conduction velocity (NCV) of the collagen + CSF group was greater than autograft group (P< 0.05). These findings showed that RPS in collagen nerve guide channel effectively enhances nerve regeneration and promotes functional recovery in injured sciatic nerve of rats.

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“…Primarily, vascular endothelial growth factor (VEGF) has an active role in the vascular tissue; however, it is determined that VEGF also has positive effects on the nerve regeneration. 106 In 2000, Hobson et al applied laminin-based gel (Matrigel) and VEGF (500-700 ng/ml) into the silicone conduit in a model in which a defect of 1 cm was formed in the rat sciatic nerve. 82 With the application of VEGF, they observed that the blood vessel penetration to around of nerve cell and Schwann cell migration have increased and the axonal regeneration has improved.…”

Section: 171mentioning

confidence: 99%

Regeneration and repair of peripheral nerves with different biomaterials: Review

2010

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Peripheral nerve injury may cause gaps between the nerve stumps. Axonal proliferation in nerve conduits is limited to 10-15 mm. Most of the supportive research has been done on rat or mouse models which are different from humans. Herein we review autografts and biomaterials which are commonly used for nerve gap repair and their respective outcomes. Nerve autografting has been the first choice for repairing peripheral nerve gaps. However, it has been demonstrated experimentally that tissue engineered tubes can also permit lead to effective nerve repair over gaps longer than 4 cm repair that was previously thought to be restorable by means of nerve graft only. All of the discoveries in the nerve armamentarium are making their way into the clinic, where they are, showing great potential for improving both the extent and rate of functional recovery compared with alternative nerve guides.

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Assessment of Axonal Growth into Collagen Nerve Guides Containing VEGF‐Transfected Stem Cells in Matrigel

Cited by 14 publications

References 57 publications

Enhancement of musculocutaneous nerve reinnervation after vascular endothelial growth factor (VEGF) gene therapy

Enhancement of musculocutaneous nerve reinnervation after vascular endothelial growth factor (VEGF) gene therapy

The Effect of Chick Embryo Cerebro-Spinal Fluid in Microwave Irradiated Collagen Guide Channel on Sciatic Nerve Regeneration in Rat

Regeneration and repair of peripheral nerves with different biomaterials: Review

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