Significant Improvement of Acute Complete Spinal Cord Injury Patients Diagnosed by a Combined Criteria Implanted with NeuroRegen Scaffolds and Mesenchymal Stem Cells

Zhifeng Xiao, Fengwu Tang, Yannan Zhao, Guang Han, Na Yin, Xing Li, Bing Chen, Sufang Han, Xianfeng Jiang, Chen Yun, Changyu Zhao, Shixiang Cheng, Sai Zhang, Jianwu Dai, Zhifeng Xiao, Fengwu Tang, Yannan Zhao, Guang Han, Na Yin, Xing Li, Bing Chen, Sufang Han, Xianfeng Jiang, Chen Yun, Changyu Zhao, Shixiang Cheng, Sai Zhang, Jianwu Dai

Abstract

Stem cells and biomaterials transplantation hold a promising treatment for functional recovery in spinal cord injury (SCI) animal models. However, the functional recovery of complete SCI patients was still a huge challenge in clinic. Additionally, there is no clinical standard procedure available to diagnose precisely an acute patient as complete SCI. Here, two acute SCI patients, with injury at thoracic 11 (T11) and cervical 4 (C4) level respectively, were judged as complete injury by a stricter method combined with American Spinal Injury Association (ASIA) Impairment Scale, magnetic resonance imaging (MRI) and nerve electrophysiology. Collagen scaffolds, named NeuroRegen scaffolds, with human umbilical cord mesenchymal stem cells (MSCs) were transplanted into the injury site. During 1 year follow up, no obvious adverse symptoms related to the functional scaffolds implantation were found after treatment. The recovery of the sensory and motor functions was observed in the two patients. The sensory level expanded below the injury level, and the patients regained the sense function in bowel and bladder. The thoracic SCI patient could walk voluntary with the hip under the help of brace. The cervical SCI patient could raise his lower legs against the gravity in the wheelchair and shake his toes under control. The injury status of the two patients was improved from ASIA A complete injury to ASIA C incomplete injury. Furthermore, the improvement of sensory and motor functions was accompanied with the recovery of the interrupted neural conduction. These results showed that the supraspinal control of movements below the injury was regained by functional scaffolds implantation in the two patients who were judged as the complete injury with combined criteria, it suggested that functional scaffolds transplantation could serve as an effective treatment for acute complete SCI patients.

Trial registration: ClinicalTrials.gov NCT02510365.

Keywords: Acute complete spinal cord injury; collagen scaffold; mesenchymal stem cells; motor recovery.

Conflict of interest statement

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

Figures

Figure 1.
Figure 1.
Patients were judged as complete injury with MRI and nerve electrophysiology. (a) MRI showed spinal cord lost its continuity at T11 segment in the thoracic SCI patient (red arrow). (b) MRI showed a total abnormal signal at the injury area in the cervical SCI patient (red arrow). (c) No SSEP of right and left tibial nerve was detected from the ankle to the cortex (1 and 3) after injury or even 2 months after surgery in the thoracic SCI patient, while the neural conduction from the ankle to the popliteal fossa was normal (2 and 4). (d) The MEP of the muscles below the injury was not detected in the thoracic SCI patient after injury. The figure showed the MEP of adductor magnus of the thoracic SCI patient. MEP: motor evoked potential; MRI: magnetic resonance imaging; SCI: spinal cord injury; SSEP: somatosensory evoked potential.
Figure 2.
Figure 2.
Intraoperative photographs of the SCI site under microscopic magnification. The images showed that the spinal cord lost its continuity and was filled with the necrosis tissue at the injured area in the thoracic SCI patient (a) and cervical SCI patient (b). (c) showed that collagen scaffolds were transplanted into the spinal cord gap of cervical SCI patient during surgery. SCI: spinal cord injury.
Figure 3.
Figure 3.
The recovery of motor function in the thoracic SCI patient after NeuroRegen scaffolds with MSCs transplantation. The hip flexors against gravity was observed. (b) The patient begun to walk under the support of brace from 6 months post-surgery. (c) The WISCI score raised with time, it was 0, 0, 3, 7 points at 1, 3, 6, 12 months post-surgery respectively. MSC: mesenchymal stem cell; SCI: spinal cord injury; WISCI: walking index for SCI.
Figure 4.
Figure 4.
The recovery of nerve electrophysiology in the thoracic SCI patient after NeuroRegen scaffolds with MSC transplantation. (a) Diagram of the recovery of SSEP and MEP. The SSEP and MEP of lower extremities could not be detected before surgery or 2 months post-surgery. The SSEP of lower extremities was detected at 4 months post-surgery. The MEP of the lower extremities reappeared on the right side at 4 months post-surgery and there was significant recovery on both sides at 12 months post-surgery. (b) The MEP of the left (upper) and right(lower) adductor magnus was significantly recovered at 12 months post-surgery. MSC: mesenchymal stem cell; SCI: spinal cord injury; SSEP: somatosensory evoked potential.
Figure 5.
Figure 5.
The recovery of the cervical SCI patient after NeuroRegen scaffolds with MSCs transplantation. (a) The patient could raise his lower leg against the gravity at 6 months post-surgery. (b) Diagram of the recovery of SSEP and MEP. The SSEP of lower extremities could be detected in left lower extremities at 2 months post-surgery, and it was detected on both sides at 6 months post-surgery accompanying with the recovery of the MEP. (c) The MEP of the left (upper) and right (lower) gastrocnemius muscles was detected at 6 months post-surgery. MEP: motor evoked potential; MSC: mesenchymal stem cell; SCI: spinal cord injury; SSEP: somatosensory evoked potential.

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