Peripheral nerve injuries are a source of chronic disability. Incomplete recovery from such injuries results in motor and sensory dysfunction and the potential for the development of chronic pain. The repair of human peripheral nerve injuries using traditional surgical techniques has limited success - particularly when a damaged nerve segment needs to be replaced. An injury to a long segment of peripheral nerve is often repaired using autologous grafting of """"""""non-critical"""""""" sensory nerve. Although extensive axonal regeneration can be observed extending into these grafts, recovery of function may be absent or incomplete, if the axons fail to reach their intended target. The goal of this exploratory/developmental R21 proposal is to develop an artificial neural prosthesis consisting of autologous Schwann cells and to facilitate translation of a promising therapy more rapidly to the clinic. Our laboratory is exploring methods to combine autologous Schwann cells isolated using cell culture techniques with axon guidance channel (AGC) technology to potentially repair critical gap lengths with in the peripheral nervous system. We utilize a very well categorized AGC which is FDA approved - but has limited application in spanning lengthy nerve gaps. Preliminary findings from our lab demonstrate robust nerve regeneration when we combine cultured autologous Schwann cells suspended in serum with a NeuraGen(R) tube to repair a lengthy gap of the rat sciatic nerve (13 mm). To test the clinical efficacy of such constructs it is critically important to characterize the fate of the transplanted Schwann cells with regards to cell survival, migration and differentiation - myelin production (Aim 1). We also seek to determine the quantity of axonal regeneration and compare to cell free channels as well with repair strategies that are currently used clinically - autologous nerve grafts (Aim 2). Finally while many nerve repair paradigms demonstrate evidence of regeneration within the AGC we seek to further determine if the regeneration observed is physiologically relevant and include electrophysiologic, behavioral and pain assessments (Aim 3). If successful, the development of this reparative approach will bring together techniques which are readily available for clinical use and should rapidly accelerate the process of bringing an effective nerve repair strategy to peripheral nerve injury patients prior to the development of pain and chronic disability.

Public Health Relevance

Following peripheral nerve injury, many patients suffer from long-lasting disability as a result of incomplete recovery of motor and sensory function. The goal of the proposed studies is to develop a nerve repair strategy consisting of an artificial neural prosthesis made of an axon guidance channel supplemented by support cells from the peripheral nervous system that have been prepared using cell culture techniques and are known to promote peripheral nerve regeneration. This novel device will be tested in rats with surgically created, long nerve gaps and the extent of nerve regeneration and functional recovery will be determined.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Exploratory/Developmental Grants (R21)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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Kleitman, Naomi
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University of Miami School of Medicine
Schools of Medicine
Coral Gables
United States
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Berrocal, Yerko A; Almeida, Vania W; Gupta, Ranjan et al. (2013) Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats. J Neurosurg 119:720-32