Safety and Efficacy of Autologous Human Schwann Cell (ahSC) Augmentation in Severe Peripheral Nerve Injury (PNI)
Abstract
As a result of the wars in Iraq and Afghanistan, a significant number of Soldiers have sustained severe peripheral nerve injuries (PNI). PNI can occur in various ways, including gunshot wounds, shrapnel from explosives and after bone fractures. The repair of large diameter nerves, particularly when a significant gap exists between the two nerve ends, represents one of the most difficult challenges in nerve surgery. The sural nerve – a small sensory nerve in the lower leg – is a common candidate for nerve grafting as it represents a non- critical nerve leaving only a relatively small area of numbness after removal. Due to a big discrepancy in cross-sectional areas between sural and other nerves, numerous sural nerve grafts must be cut, layered, and sutured across to bridge large traumatic defects. Despite the availability of various treatment options, we are still lacking the optimal treatments for a perfect and complete functional regain. The need for the present age is to discover or design such therapy that would be able to execute the complete functional retrieval. The proposed therapy will advance tissue regeneration in nerve for the restoration of traumatically injured extremities. Our phase I clinical trial will confirm feasibility and potential efficacy involving volumetric muscle loss. Considering Alternative Options: The use of Schwann cells (SCs) to restore traumatic nerve defects has been extremely promising. A multitude of preclinical data has shown that adding SCs to nerve repair leads to enhanced recovery, both functionally and histologically. These SCs provide supportive growth signals to budding axons from the injured distal stump. Such cells can be harvested from a small nerve biopsy in a patient with severe nerve injury while planning surgical repair. The process of regeneration initiates with the reversal of all retrograde degenerative changes. As the SCs stop making myelin, they cause macrophage activation, which leads to the phagocytosis of myelin sheath deposits. In addition to clearing myelin debris, macrophages and SCs also produce cytokines to promote axonal growth. As debris clears, the regeneration starts at the proximal end of the injured site and continues toward the distal end. The SCs play a role in guiding the cytoplasmic extensions of the axonal sprout between the basement membranes of two nerve ends. Additionally, they act to recycle and digest proteins and lipids of the injured nerve tissue. We hypothesize that by adding the patient’s own cells expanded in the lab to a nerve repair construct, i.e., severed nerve stumps connected by intervening sural nerve grafts, we can promote more rapid and robust axonal recovery. Further, by wrapping the repaired segment and transplanted cells with a slow-absorbing collagen wrap we can sequester this pro-growth environment for the duration of the recovery. Evidence also suggests that this wrap may prevent abhorrent growth of nerve fibers and thereby reduce neuropathic pain. The proposed study will investigate the use of nerve-derived, autologous human Schwann cells and their ability to supplement nerve graft repair (the current gold standard). The proposed clinical investigations will provide necessary data on the critical information on cell delivery, dosing, and the regenerative effects of SC implantation within enveloped nerve repairs. This study will be conducted at the University of Miami Department of Neurological Surgery and the Lois Pope Life Center to Cure Paralysis, in conjunction with the Interdisciplinary Stem Cell Institute. The study will span a 4-year period and will utilize multiple outcome metrics both clinical and radiographic. With the help of clinicians and researchers from the Radiology Department, we will use novel magnetic resonance (MR) imaging techniques, namely diffusion imaging. Diffusion Tensor Imaging (DTI): DTI has recently been shown helpful in assessing axonal recovery after injury. By
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211048
Entities
People
- Allan D Levi
Organizations
- United States Army
- University of Miami