Autologous Schwann Cell Therapy for Peripheral Nerve Injury
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: W. Dalton Dietrich
Disqualifiers: Pregnancy, Substance abuse, HIV, others
No Placebo Group
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?The primary purpose of this research study is to evaluate the safety and possible harms of injecting one's own Schwann cells along with nerve auto-graft after a severe injury to a major nerve has occurred.
Do I have to stop taking my current medications for the trial?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the treatment Autologous Human Schwann Cell for peripheral nerve injury?
Research shows that Schwann cell transplantation can promote nerve regeneration and repair in both peripheral and central nervous systems. Studies have demonstrated improvements in motor and sensory functions in patients with spinal cord injuries after receiving autologous Schwann cell transplants, suggesting potential effectiveness for peripheral nerve injuries as well.
12345Is autologous Schwann cell therapy safe for humans?
Research indicates that autologous Schwann cell therapy is generally safe for humans, as studies have shown no serious adverse effects or complications related to the therapy in patients with spinal cord injuries. Some patients experienced temporary sensations like tingling or muscle spasms, but no long-term safety issues were reported.
13678How is Autologous Schwann Cell Therapy different from other treatments for peripheral nerve injury?
Autologous Schwann Cell Therapy is unique because it uses the patient's own Schwann cells, which are specialized cells that support nerve repair, to promote healing of peripheral nerve injuries. This approach is different from other treatments as it involves transplanting these cells directly to the injury site, potentially enhancing nerve regeneration and reducing the risk of immune rejection.
234910Eligibility Criteria
This trial is for adults aged 18-65 who have had a severe nerve injury in the past year, such as sciatic or brachial plexus injuries. It's not for pregnant women, those with certain pre-existing conditions, allergies to gentamicin, HIV/Hepatitis B/C, cognitive impairments that prevent consent, or if the nerve gap is over 10 cm.Participant Groups
The study tests injecting patients' own Schwann cells into their injured nerves alongside a standard nerve grafting procedure. The goal is to see if this approach improves recovery from severe peripheral nerve injuries.
1Treatment groups
Experimental Treatment
Group I: Autologous Human Schwann Cell (ahSC) GroupExperimental Treatment1 Intervention
Participants in this group will undergo a sural nerve biopsy followed by ahSC transplant
Autologous Human Schwann Cell is already approved in United States, China for the following indications:
πΊπΈ Approved in United States as Autologous Human Schwann Cell for:
- Severe Peripheral Nerve Injury (PNI)
- Spinal Cord Injury (SCI)
π¨π³ Approved in China as Autologous Human Schwann Cell for:
- Spinal Cord Injury (SCI)
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of MiamiMiami, FL
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Who is running the clinical trial?
W. Dalton DietrichLead Sponsor
United States Department of DefenseCollaborator
References
Autologous adult human Schwann cells genetically modified to provide alternative cellular transplants in peripheral nerve regeneration. [2006]The purpose of this study was to provide genetically modified adult human Schwann cells as tools for cell transplantation in peripheral nerve repair. The application of transfected autologous Schwann cells overexpressing regeneration-promoting proteins, for example, neurotrophic or growth factors, is a promising approach in the aforementioned context. To achieve an optimal clinical outcome, it is highly important to perform enrichment, genetic modification, and retransplantation of cells in a short time.
Schwann cell transplantation and myelin repair of the CNS. [2017]Studies with experimental models of dysmyelination and demyelination have shown that rodent Schwann cells including a Schwann cell line, transplanted in the central nervous system compete with host oligodendrocytes to remyelinate denuded central axons of the spinal cord. The myelin produced by transplanted SC around these central nervous system axons is structurally normal and restores, secure nerve conduction. In the presence of a favorable substrate, transplanted Schwann cells migrate over considerable distances (several mm) and are recruited by a demyelinated lesion which they will partially repair Thus Schwann cells, which can also support axonal growth, may be instrumental in central nervous system repair. In addition, the possibility of obtaining large quantities of human and non-human primate Schwann cells, makes it possible to consider autologous Schwann cell transplantation as a potential therapy for demyelinating or traumatic diseases. The various differences which may exist between rodents and humans, however, require further investigation of this possibility in a non-human primate model of demyelination. These experiments should provide not only insights on the potential of autologous transplantation in primates but also a better understanding of the process of central remyelination.
Transplantation of autologous activated Schwann cells in the treatment of spinal cord injury: six cases, more than five years of follow-up. [2022]Schwann cells (SCs) are the main glial cells of the peripheral nervous system, which can promote neural regeneration. Grafting of autologous SCs is one of the well-established and commonly performed procedures for peripheral nerve repair. With the aim to improve the clinical condition of patients with spinal cord injury (SCI), a program of grafting autologous activated Schwann cells (AASCs), as well as a series of appropriate neurorehabilitation programs, was employed to achieve the best therapeutic effects. We selected six patients who had a history of SCI before transplantation. At first, AASCs were obtained by prior ligation of sural nerve and subsequently isolated, cultured, and purified in vitro. Then the patients accepted an operation of laminectomy and cell transplantation, and no severe adverse event was observed in any of these patients. Motor and sensitive improvements were evaluated by means of American Spinal Injury Association (ASIA) grading and Functional Independence Measure (FIM); bladder and urethral function were determined by clinical and urodynamic examination; somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) were used to further confirm the functional recovery following transplantation. The patients were followed up for more than 5 years. All of the patients showed some signs of improvement in autonomic, motor, and sensory function. So we concluded that AASC transplantation might be feasible, safe, and effective to promote neurorestoration of SCI patients.
Schwann cell cultures: recent advances and novel approaches to the reconstruction of peripheral nerve defects. [2012]Current techniques in tissue engineering may offer a choice regarding the reconstructive strategies of peripheral nerves. Schwann cell cultures are to be considered an appropriate option in the reconstruction of peripheral nerve and spinal cord large defects. Schwann cells availability from peripheral nerve autografts creates a great benefit concerning their usefulness in the nervous autogenic transplantation. Allogeneic Schwann cells transplantation can be effective in the reconstruction without delay of peripheral nerve defects.
From transplanting Schwann cells in experimental rat spinal cord injury to their transplantation into human injured spinal cord in clinical trials. [2018]Among the potential therapies designed to repair the injured spinal cord is cell transplantation, notably the use of autologous adult human Schwann cells (SCs). Here, we detail some of the critical research accomplished over the last four decades to establish a foundation that enables these cells to be tested in clinical trials. New culture systems allowed novel information to be gained about SCs, including discovering ways to stimulate their proliferation to acquire adequately large numbers for transplantation into the injured human spinal cord. Transplantation of rat SCs into rat models of spinal cord injury has demonstrated that SCs promote repair of injured spinal cord. Additional work required to gain approval from the Food and Drug Administration for the first SC trial in the Miami Project is disclosed. This trial and a second one now underway are described.
Safety of Autologous Human Schwann Cell Transplantation in Subacute Thoracic Spinal Cord Injury. [2022]The rationale for implantation of autologous human Schwann cells (SCs) in persons with subacute spinal cord injury (SCI) is based on evidence that transplanted SCs are neuroprotective, support local axonal plasticity, and are capable of myelinating axons. A Phase I clinical trial was conducted to evaluate the safety of autologous human SC transplantation into the injury epicenter of six subjects with subacute SCI. The trial was an open-label, unblinded, non-randomized, non-placebo controlled study with a dose escalation design and standard medical rehabilitation. Participants were paraplegics with neurologically complete, trauma-induced spinal lesions. Autologous SCs were cultured in vitro from a sural nerve harvested from each participant and injected into the epicenter of the spinal lesion. Outcome measures for safety were protocol compliance, feasibility, adverse events, stability of neurological level, absence of detectable mass lesion, and the emergence of clinically significant neuropathic pain or muscle spasticity no greater than expected for a natural course cohort. One year post-transplantation, there were no surgical, medical, or neurological complications to indicate that the timing or procedure for the cell transplantation was unsafe. There were no adverse events or serious adverse events related to the cell therapy. There was no evidence of additional spinal cord damage, mass lesion, or syrinx formation. We conclude that it is feasible to identify eligible candidates, appropriately obtain informed consent, perform a peripheral nerve harvest to obtain SCs within 5-30 days of injury, and perform an intra-spinal transplantation of highly purified autologous SCs within 4-7 weeks of injury.
Treatment of chronic thoracic spinal cord injury patients with autologous Schwann cell transplantation: an interim report on safety considerations and possible outcomes. [2008]Several experimental studies have introduced Schwann cell transplantation as a means of recovery in animal models of spinal cord injury (SCI). The reported promising results together with the availability of autologous sources for Schwann cells indicate Schwann cell transplantation as a possible treatment for SCI. To address the safety and feasibility concerns we report 1-year follow-up of four patients aged between 22 and 43 years who had stable chronic (28-80 months) spinal cord injury at mid-thoracic level and treated with autologous Schwann cell transplantation. Purified Schwann cells used for transplantation were acquired from autologous sural nerve and cultured without the use of any specific mitogenic or growth factors. The patients were evaluated by means of American Spinal Injury Association (ASIA) criteria, sphincter, sexual function and Magnetic Resonance Imaging assessments for 1 year after transplantation. None of the patients were found to have any adverse effects indicating transfer of infection, neurological deterioration or other related clinical problems. Of the four patients, only one patient with incomplete SCI showed motor and sensory improvement 1 year after transplantation with extensive and continuous rehabilitation. All the four patients experienced transient paresthesia or increased muscle spasm after transplantation. Magnetic Resonance (MR) images of the patients did not show any visible changes or pathological findings after 1 year. This preliminary report shows that autologous Schwann cell transplantation is generally safe for the selected number of SCI patients but it does not prove beneficial effects. Further safety and outcome studies are recommended.
Clinical grade cultivation of human Schwann cell, by the using of human autologous serum instead of fetal bovine serum and without growth factors. [2012]Clinical grade cultivation of human schwann cell by the utilization of human autologous serum instead of fetal bovine serum, and also avoiding any growth factors, can increase safety level of this procedure in cases of clinical cell transplantation. The aim of this study was demonstration of the feasibility of clinical grade schwann cell cultivation. In this experimental study after obtaining consent from close relatives we harvested 10 sural nerves from brain death donors and then cultured in 10 seperated culture media plus autologous serum. We also prepared autologous serum from donor's whole blood. Then cultured cells were evaluated by S100 antibody staining for both morphology and purity. Cell purity range was from 97% to 99% (mean=98.11 Β± 0.782%). Mean of the cell count was 14,055.56 Β± 2,480.479 per micro liter. There was not significant correlation between cell purity and either the culture period or the age of donors (P>0.05). The spearman correlation coefficient for the cell purity with the period or the age of donors was 0.21 and 0.09, respectively. We demonstrated the feasibility of clinical grade schwann cell cultivation by the using of human autologous serum instead of fetal bovine serum and also without the using of growth factors. We also recommended all cell preparation facilities to adhere to the GMP and other similar quality disciplines especially in the preparation of clinically-used cell products.
Therapeutic strategies for peripheral nerve injury: decellularized nerve conduits and Schwann cell transplantation. [2020]In recent years, the use of Schwann cell transplantation to repair peripheral nerve injury has attracted much attention. Animal-based studies show that the transplantation of Schwann cells in combination with nerve scaffolds promotes the repair of injured peripheral nerves. Autologous Schwann cell transplantation in humans has been reported recently. This article reviews current methods for removing the extracellular matrix and analyzes its composition and function. The development and secretory products of Schwann cells are also reviewed. The methods for the repair of peripheral nerve injuries that use myelin and Schwann cell transplantation are assessed. This survey of the literature data shows that using a decellularized nerve conduit combined with Schwann cells represents an effective strategy for the treatment of peripheral nerve injury. This analysis provides a comprehensive basis on which to make clinical decisions for the repair of peripheral nerve injury.
Differentiated human adipose-derived stromal cells exhibit the phenotypic and functional characteristics of mature Schwann cells through a modified approach. [2020]Tissue engineering technology is a promising therapeutic strategy in peripheral nerve injury. Schwann cells (SCs) are deemed to be a vital component of cell-based nerve regeneration therapies. Many methods for producing SC-like cells derived from adipose-derived stromal cells (ADSCs) have been explored, but their phenotypic and functional characteristics remain unsatisfactory.