Combining cell therapy with human autologous Schwann cell and bone marrow-derived mesenchymal stem cell in patients with subacute complete spinal cord injury: safety considerations and possible outcomes

Abstract

Background Cellular transplantations have promising effects on treating spinal cord injury (SCI) patients. Mesenchymal stem cells (MSCs) and Schwann cells (SCs), which have safety alongside their complementary characteristics, are suggested to be the two of the best candidates in SCI treatment. In this study, we assessed the safety and possible outcomes of intrathecal co-transplantation of autologous bone marrow MSC and SC in patients with subacute traumatic complete SCI. Methods Eleven patients with complete SCI (American Spinal Injury Association Impairment Scale (AIS); grade A) were enrolled in this study during the subacute period of injury. The patients received an intrathecal autologous combination of MSC and SC and were followed up for 12 months. We assessed the neurological changes by the American Spinal Injury Association’s (ASIA) sensory-motor scale, functional recovery by spinal cord independence measure (SCIM-III), and subjective changes along with adverse events (AE) with our checklist. Furthermore, electromyography (EMG), nerve conduction velocity (NCV), magnetic resonance imaging (MRI), and urodynamic study (UDS) were conducted for all the patients at the baseline, 6 months, and 1 year after the intervention. Results Light touch AIS score alterations were approximately the same as the pinprick changes (11.6 ± 13.1 and 12 ± 13, respectively) in 50% of the cervical and 63% of the lumbar-thoracic patients, and both were more than the motor score alterations (9.5 ± 3.3 in 75% of the cervical and 14% of the lumbar-thoracic patients). SCIM III total scores (21.2 ± 13.3) and all its sub-scores (“respiration and sphincter management” (15 ± 9.9), “mobility” (9.5 ± 13.3), and “self-care” (6 ± 1.4)) had statistically significant changes after cell injection. Our findings support that the most remarkable positive, subjective improvements were in trunk movement, equilibrium in standing/sitting position, the sensation of the bladder and rectal filling, and the ability of voluntary voiding. Our safety evaluation revealed no systemic complications, and radiological images showed no neoplastic overgrowth, syringomyelia, or pseudo-meningocele. Conclusion The present study showed that autologous SC and bone marrow-derived MSC transplantation at the subacute stage of SCI could reveal statistically significant improvement in sensory and neurological functions among the patients. It appears that using this combination of cells is safe and effective for clinical application to spinal cord regeneration during the subacute period.

Safety and Clinical Efficacy of Mesenchymal Stem Cell Treatment in Traumatic Spinal Cord Injury, Multiple Sclerosis and Ischemic Stroke – A Systematic Review and Meta-Analysis

“…Of the 26 included studies, seven were controlled ( 49 – 55 ), of which five were randomized ( 49 , 51 , 52 , 54 , 55 ), one double-blinded ( 55 ) and two assessor-blinded ( 51 , 52 ). Fourteen studies included patients with isolated AIS A ( 17 – 19 , 22 , 24 , 25 , 27 , 30 , 32 , 50 – 53 , 55 ), one isolated AIS B ( 20 ) whereas 11 studies included all AIS classifications or did not specify this in the inclusion criteria ( 14 – 16 , 21 , 23 , 26 , 28 , 29 , 31 , 49 , 54 ). Four studies included only patients with cervical injury ( 16 , 20 , 51 , 53 ) and five included only patients with thoracic injury ( 22 , 25 , 32 , 50 , 55 ).…”

“…According to inclusion criteria, MSC treatment was administered within the first 3 weeks after injury in one study ( 53 ), within 2–8 weeks in one study ( 50 ) and after 6 months or more in 13 studies ( 18 – 21 , 24 – 26 , 28 , 29 , 32 , 51 , 55 ). Twelve studies used intralesional administration via surgery or guided injections ( 14 , 18 – 20 , 25 , 27 , 29 , 32 , 51 – 54 ) and ten studies administered the cells intrathecally via lumbar puncture ( 15 , 21 – 23 , 26 , 28 , 30 , 31 , 50 , 55 ), whereas four used combinations of different administration methods ( 16 , 17 , 24 , 49 ).…”

Clinical translation of stem cell therapy for spinal cord injury still premature: results from a single-arm meta-analysis based on 62 clinical trials

“…Among the many safety issues surrounding stem cell transplantation, tumorigenesis is much more worrying than the fever and neuropathic pain caused by mild immune or allergic reactions [ 56 , 79 ]. Stem cell products derived from hESCs and iPSCs confer the highest risk of tumorigenesis due to the presence of residual undifferentiated stem cells, malignantly transformed cells/mutations, and genetic instability.…”

The Effect of Schwann Cells/Schwann Cell-Like Cells on Cell Therapy for Peripheral Neuropathy

“…Most studies have been focused on evaluating safety and adverse events after transplantation ( Yazdani et al, 2013 ; Mendonca et al, 2014 ; Anderson et al, 2017 ; Gant et al, 2021 ). Notably, single MSC administration is safe but less effective than combination treatment with autologous Schwann cells ( Oh et al, 2016 ), which improves sensory and motor functional recovery to some extent, as well as bladder compliance ( Oraee-Yazdani et al, 2016 , 2021 ). In addition, the administration of these cells by intravenous infusion, intrathecal administration or direct injection into spinal lesions, and the injury level and size may lead to different outcomes.…”