NeuroRegen Scaffolds Combined with Autologous Bone Marrow Mononuclear Cells for the Repair of Acute Complete Spinal Cord Injury: A 3-Year Clinical Study

Wugui Chen, Ying Zhang, Sizhen Yang, Jing Sun, Hao Qiu, Xu Hu, Xiaojian Niu, Zhifeng Xiao, Yannan Zhao, Yue Zhou, Jianwu Dai, Tongwei Chu, Wugui Chen, Ying Zhang, Sizhen Yang, Jing Sun, Hao Qiu, Xu Hu, Xiaojian Niu, Zhifeng Xiao, Yannan Zhao, Yue Zhou, Jianwu Dai, Tongwei Chu

Abstract

Spinal cord injury (SCI) remains among the most challenging pathologies worldwide and has limited therapeutic possibilities and a very bleak prognosis. Biomaterials and stem cell transplantation are promising treatments for functional recovery in SCI. Seven patients with acute complete SCI diagnosed by a combination of methods were included in the study, and different lengths (2.0-6.0 cm) of necrotic spinal cord tissue were surgically cleaned under intraoperative neurophysiological monitoring. Subsequently, NeuroRegen scaffolds loaded with autologous bone marrow mononuclear cells (BMMCs) were implanted into the cleaned site. All patients participated in 6 months of rehabilitation and at least 3 years of clinical follow-up. No adverse symptoms associated with stem cell or functional scaffold implantation were observed during the 3-year follow-up period. Additionally, partial shallow sensory and autonomic nervous functional improvements were observed in some patients, but no motor function recovery was observed. Magnetic resonance imaging suggested that NeuroRegen scaffold implantation supported injured spinal cord continuity after treatment. These findings indicate that implantation of NeuroRegen scaffolds combined with stem cells may serve as a safe and promising clinical treatment for patients with acute complete SCI. However, determining the therapeutic effects and exact application methods still requires further study.

Trial registration: ClinicalTrials.gov NCT02510365.

Keywords: NeuroRegen scaffold; acute complete spinal cord injury; autologous bone marrow mononuclear cells; regeneration.

Conflict of interest statement

Declaration of Conflicting Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Fig. 1.
Fig. 1.
Intraoperative neuroelectrophysiological monitoring was used to determine the extent of spinal cord injury (the left side shows the caudal segments, and the right side shows cephalad segments). (A, B) The signal-receiving electrode was placed on the normal spinal cord, and the stimulation electrode was moved slowly from the injured side to the normal side until the extent of the normal spinal cord in the caudal segments was determined. (C) The same method was used to determine the extent of spinal cord injury in the cephalad segments.
Fig. 2.
Fig. 2.
Injured spinal cords were cleaned, followed by functional NeuroRegen scaffold implantation. (A) Diffuse hyperemia, edema, and tissue necrosis were observed at the site of spinal cord injury after the dura mater was opened. (B) After determining the boundaries of the injured spinal cord by neuroelectrophysiological monitoring, the necrotic spinal cord tissue was cleaned. (C, D) Extracted autologous bone marrow mononuclear cells were evenly spread over the surface of the NeuroRegen scaffolds and grafted into the cleaned spinal cord gap. (E) Biogel was evenly injected onto the scaffolds. (F) The dura mater was tightly sutured.
Fig. 3.
Fig. 3.
Preoperative and postoperative CT and MRI images of patients with acute complete spinal cord injury who underwent functional NeuroRegen scaffold implantation. (A) Preoperative and postoperative CT images. (B) MRI images of preoperatively, postoperatively, and 6 and 36 months after surgery. CT: computed tomography; MRI: magnetic resonance imaging.

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