Neuroma Formation in a Rat Median Nerve Model: Influence of Distal Stump and Muscular Coating

Sinis, Nektarios; Haerle, Max; Becker, Stephan; Schulte-Eversum, C.; Vonthein, Reinhard; Rösner, Harald; Schaller, Hans-Eberhard

doi:10.1097/01.prs.0000242486.70919.82

Cited by 26 publications

(16 citation statements)

References 26 publications

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“…Autologous nerve grafts are generally utilized to repair severe lesions; however, this results in permanent loss of donor nerve function and is inadequate to repair extensive nerve damage due to limited availability. 1,2 While alternative clinical approaches include synthetic tubes, such conduits are only effective for relatively small peripheral nerve (PN) gaps. 3,4 Moreover, no current strategy addresses gradual degeneration of support cells in the nerve segment distal to the injury site, which severely limits recovery of function due to the loss of cues to guide axonal regeneration beyond the lesion.…”

Section: Introductionmentioning

confidence: 99%

Long-Term Survival and Integration of Transplanted Engineered Nervous Tissue Constructs Promotes Peripheral Nerve Regeneration

Huang

Cullen

Browne

et al. 2009

Tissue Engineering Part A

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Although peripheral nerve injury is a common consequence of trauma or surgery, there are insufficient means for repair. In particular, there is a critical need for improved methods to facilitate regeneration of axons across major nerve lesions. Here, we engineered transplantable living nervous tissue constructs to provide a labeled pathway to guide host axonal regeneration. These constructs consisted of stretch-grown, longitudinally aligned living axonal tracts inserted into poly(glycolic acid) tubes. The constructs (allogenic) were transplanted to bridge an excised segment of sciatic nerve in the rat, and histological analyses were performed at 6 and 16 weeks posttransplantation to determine graft survival, integration, and host regeneration. At both time points, the transplanted constructs were found to have maintained their pretransplant geometry, with surviving clusters of graft neuronal somata at the extremities of the constructs spanned by tracts of axons. Throughout the transplanted region, there was an intertwining plexus of host and graft axons, suggesting that the transplanted axons mediated host axonal regeneration across the lesion. By 16 weeks posttransplant, extensive myelination of axons was observed throughout the transplant region. Further, graft neurons had extended axons beyond the margins of the transplanted region, penetrating into the host nerve. Notably, this survival and integration of the allogenic constructs occurred in the absence of immunosuppression therapy. These findings demonstrate the promise of living tissue-engineered axonal constructs to bridge major nerve lesions and promote host regeneration, potentially by providing axon-mediated axonal outgrowth and guidance.

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Section: Introductionmentioning

confidence: 99%

Long-Term Survival and Integration of Transplanted Engineered Nervous Tissue Constructs Promotes Peripheral Nerve Regeneration

Huang

Cullen

Browne

et al. 2009

Tissue Engineering Part A

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show abstract

“…Previously, a naturally occurring small molecule was discovered that antagonizes sema3A and promotes recovery of function in a rat model of spinal cord injury (Kaneko et al, 2006). Progress in creating an animal model for the peripheral nerve neuroma (Sinis et al, 2007) will allow future studies on the effect of this compound on axonal regeneration through neuroma tissue. Such studies could lead to novel strategies that may be applied as an adjuvant therapy to peripheral nerve surgery.…”

Section: Discussionmentioning

confidence: 99%

Human Neuroma Contains Increased Levels of Semaphorin 3A, Which Surrounds Nerve Fibers and Reduces Neurite ExtensionIn Vitro

Tannemaat

Korecka²,

Ehlert³

et al. 2007

J. Neurosci.

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Neuroma formation after peripheral nerve injury is detrimental to functional recovery and is therefore a significant clinical problem. The molecular basis for this phenomenon is not fully understood. Here, we show that the expression of the chemorepulsive protein semaphorin 3A (sema3A), but not semaphorin 3F, is increased in human neuroma tissue that has formed in severe obstetric brachial plexus lesions. Sema3A is produced by fibroblasts in the epineurial space and appears to be secreted into the extracellular matrix. It surrounds fascicles, minifascicles, or single axons, suggesting a role in fasciculation and inhibition of neurite outgrowth. Lentiviral vector-mediated knock-down of Neuropilin 1, the receptor for sema3A, leads to increased neurite outgrowth of F11 cells cultured on neuroma tissue, but not of F11 cells cultured on normal nerve tissue. These findings demonstrate the putative inhibitory role of sema3A in human neuroma tissue. Our observations are the first demonstration of the expression of sema3A in human neural scar tissue and support a role for this protein in the inhibition of axonal regeneration in injured human peripheral nerves. These findings contribute to the understanding of the outgrowth inhibitory properties of neuroma tissue.

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“…For light microscopy assessment, neuroma-like cross-sectional area was measured on Masson's stained sections using point counting technique similar to the technique proposed by Sinis et al 18 For confocal laser microscopy assessment, a semi-quantitative evaluation of the axo-glial cytoarchitecture was given to all nerve specimens by the same observer. Each specimen was given a score on a scale ranging from 0 to 4, where 0 is completely disorganized and 4 is normal organization of the axo-glial complex.…”

Section: Quantitative Morphological Analysismentioning

confidence: 99%

A free vein graft cap influences neuroma formation after nerve transection

et al. 2009

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: Our results confirm that vein-covering of a transected nerve stump can be effective in reducing neuroma formation. Moreover, unlike previous works that buried the nerve into an adjacent vein left in place, our experiments showed that also the use of a free vein graft cap can hinder neuroma formation. Although translation of rat experiments to the clinics should be dealt with caution, our data suggest a careful clinical use of the technique. (c) 2009 Wiley-Liss, Inc. Microsurgery, 2009.

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Neuroma Formation in a Rat Median Nerve Model: Influence of Distal Stump and Muscular Coating

Cited by 26 publications

References 26 publications

Long-Term Survival and Integration of Transplanted Engineered Nervous Tissue Constructs Promotes Peripheral Nerve Regeneration

Long-Term Survival and Integration of Transplanted Engineered Nervous Tissue Constructs Promotes Peripheral Nerve Regeneration

Human Neuroma Contains Increased Levels of Semaphorin 3A, Which Surrounds Nerve Fibers and Reduces Neurite ExtensionIn Vitro

A free vein graft cap influences neuroma formation after nerve transection

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