One-year clinical study of NeuroRegen scaffold implantation following scar resection in complete chronic spinal cord injury patients

Abstract

The objective of this clinical study was to assess the safety and feasibility of the collagen scaffold, NeuroRegen scaffold, one year after scar tissue resection and implantation. Scar tissue is a physical and chemical barrier that prevents neural regeneration. However, identification of scar tissue is still a major challenge. In this study, the nerve electrophysiology method was used to distinguish scar tissue from normal neural tissue, and then different lengths of scars ranging from 0.5-4.5 cm were surgically resected in five complete chronic spinal cord injury (SCI) patients. The NeuroRegen scaffold along with autologous bone marrow mononuclear cells (BMMCs), which have been proven to promote neural regeneration and SCI recovery in animal models, were transplanted into the gap in the spinal cord following scar tissue resection. No obvious adverse effects related to scar resection or NeuroRegen scaffold transplantation were observed immediately after surgery or at the 12-month follow-up. In addition, patients showed partially autonomic nervous function improvement, and the recovery of somatosensory evoked potentials (SSEP) from the lower limbs was also detected. The results indicate that scar resection and NeuroRegen scaffold transplantation could be a promising clinical approach to treating SCI.NeuroRegen scaffold, chronic spinal cord injury, scar resection, collagen scaffold transplantation, bone marrow mononuclear cells, tissue regeneration Citation:Xiao, Z., Tang, F., Tang, J., Yang, H., Zhao, Y., Chen, B., Han, S., Wang, N., Li, X., Cheng, S., Han, G., Zhao, C., Yang, X., Chen, Y., Shi, Q., Hou, S., Zhang, S., and Dai, J. (2016). One-year clinical study of NeuroRegen scaffold implantation following scar resection in complete chronic spinal cord injury patients. Sci China Life Sci 59, 647 -655.

Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses

“…Preliminary results of the phase I trial in eight patients receiving MSCs with complete chronic SCI report partial recovery of motor function in three patients and changes in autonomic function in six patients with no adverse effects 1 year after surgery [104]. Similar results were reported from 5 patients that received BMMCs, there were no significant adverse effects for 12 months postoperatively and 2 individuals had partial recovery of sexual arousal and somatosensory evoked potentials [103]. Researchers have tested difference biomaterials and cellular sources in preclinical models with promising results, further demonstrating the therapeutic potential of targeting the glial and fibrotic scar after SCI [105].…”

“…A clinical illustration of this approach comes from a small, ongoing phase I trial in China (ClinicalTrials.gov: NCT02352077) [103,104]. The goal of the clinical trial is to create a permissive extracellular environment through transplantation of a linearly oriented scaffold that serves both as a delivery tool for bone marrow mononuclear cells (BMMCs) [103] or mesenchymal stem cells (MSC) [104] and to orient axon regeneration across the injured spinal cord. The combinatorial approach has the potential to overcome endogenous molecular and physical ECM barriers after SCI.…”

Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair

“…Thus, a combinatorial approach is urgently needed. Various combinatorial approaches involving drugs and interventions including Chondroitinase ABC (ChABC)/neurotrophic factors 50 , cells/neurotrophic factors 51 , 52 , and anti-myelin-associated glycoproteins (MAG)/other anti-inhibitory factors 51 , 53 , 54 , have been proposed for effective regeneration after SCI. Nevertheless, most of them are neuroprotective and do not promote the restoration of severed axonal connections, or they try to overcome only one of the obstacles to regeneration.…”

Holistic Approach to Axonal Regeneration in Cases of Spinal Cord Injury

“…However, it should be considered the influence of enhancement factors that had been incorporated into implantable nanofabricated polymers, such as extracellular matrix, growth and neurotrophic factors, as well as other materials capable of modulating remyelination, axonal regeneration, and neurological recovery [84][85][86][87][88][89][90][91][92]. Bio-absorbable materials have an advantage in the covering of cofactors; these are released by degradation and have a controlled release effect [79].…”