Safety of Autologous Human Schwann Cell Transplantation in Subacute Thoracic Spinal Cord Injury

Abstract

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.

Human Schwann cells exhibit long‐term cell survival, are not tumorigenic and promote repair when transplanted into the contused spinal cord

“…Lastly, the ability of HuSCs to support axon growth and myelination was examined. The data presented herein formed part of the preclinical safety studies used in support of IND 14856 that sought to investigate the safety and efficacy of autologous SC transplantation in a Phase 1 Clinical Trial for sub‐acute, complete human thoracic SCI (Anderson et al, ) (http://clinicaltrials.gov/show/NCT01739023).…”

Time‐restricted release of multiple neurotrophic factors promotes axonal regeneration and functional recovery after peripheral nerve injury

“…SCs transplantation has emerged as a promising therapy for both PNS and CNS injury. Recently, several clinical centers have tested autologous SCs in clinical trials for treatment of CNS injury (60)(61)(62)(63). In PNS injury, SC transplantation has shown better nerve regeneration than those without SCs in a big-animal model, especially for long-gap peripheral nerve injury (64).…”

Current Status and Future Strategies to Treat Spinal Cord Injury with Adult Stem Cells

“…In most of the clinical trials presented in Tables 1-3, researchers reported that their clinical trials were safe without mortalities or severe morbidities related to either procedures or transplanted cells. However, there were some reported complications which were not associated with the procedures or applied cells : fever 4,40,59,64) , urinary tract infection 2,19,27,59) , abnormal blood profiles 2,27,40,45) , transient hypertension 26) , vomiting 4,19) , pulmonary thromboembolism 27) , and general body ache 4) . On the contrary, some complications including transient neuropathic pain 2,26,27,29,37,67) , transient deterioration in sensorimotor symptoms 29,37,44,64) , cerebrospinal f luid leakage 67) , subarachnoid hemorrhage 67) and subcutaneous seroma 67) , might be related to stem cell delivering procedures.…”

“…Transplanted Schwann cells (SCs) alter the inhibitory glial environment and induce axonal regeneration in SCI 22) . SCs are safe and there are no reports of malignant transformation or any other significant complications with these cells 2) . However, it is challenging to isolate SCs due to the risk of damaging other peripheral nerve segments, resulting in undesirable iatrogenic injury at the donor site 60) .…”