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

Abstract

Background How much scientific evidence is there to show that stem cell therapy is sufficient in preclinical and clinical studies of spinal cord injury before it is translated into clinical practice? This is a complicated problem. A single, small-sample clinical trial is difficult to answer, and accurate insights into this question can only be given by systematically evaluating all the existing evidence. Methods The PubMed, Ovid-Embase, Web of Science, and Cochrane databases were searched from inception to February 10, 2022. Two independent reviewers performed the literature search, identified and screened the studies, and performed a quality assessment and data extraction. Results In total, 62 studies involving 2439 patients were included in the analysis. Of these, 42 were single-arm studies, and 20 were controlled studies. The meta-analysis showed that stem cells improved the ASIA impairment scale score by at least one grade in 48.9% [40.8%, 56.9%] of patients with spinal cord injury. Moreover, the rate of improvement in urinary and gastrointestinal system function was 42.1% [27.6%, 57.2%] and 52.0% [23.6%, 79.8%], respectively. However, 28 types of adverse effects were observed to occur due to stem cells and transplantation procedures. Of these, neuropathic pain, abnormal feeling, muscle spasms, vomiting, and urinary tract infection were the most common, with an incidence of > 20%. While no serious adverse effects such as tumorigenesis were reported, this could be due to the insufficient follow-up period. Conclusions Overall, the results demonstrated that although the efficacy of stem cell therapy is encouraging, the subsequent adverse effects remain concerning. In addition, the clinical trials had problems such as small sample sizes, poor design, and lack of prospective registration, control, and blinding. Therefore, the current evidence is not sufficiently strong to support the clinical translation of stem cell therapy for spinal cord injury, and several problems remain. Additional well-designed animal experiments and high-quality clinical studies are warranted to address these issues.

Hydrogel scaffolds in the treatment of spinal cord injury: a review

“…Current advances in stem cell and neuroregenerative science research hold the promise of a complete cure for SCI. A meta-analysis based on 62 clinical trials found that although the efficacy of cell therapy is encouraging, its adverse effects are still a concern ( Shang et al, 2022 ). Hydrogels have been shown in clinical trials to be used in combination with stem cells in the treatment of SCI to improve the microenvironment at the injury, provide support for cell proliferation and migration, and compensate for the inadequacy of cell transplantation therapy alone.…”

Immune response following traumatic spinal cord injury: Pathophysiology and therapies

“…Clinical trials, preclinical studies, and meta-analyses have shown that although the efficacy of stem cell therapy is promising, many challenges remain which will require further optimization and innovative solutions (293). One of the biggest and most concerning challenges of stem cell therapy for spinal cord injury moving forward is the potential for adverse effects.…”

“…Although many clinical trials have been reported as safe without mortalities or severe morbidity, tumorigenicity, immunogenicity, and cell therapy-related immunotoxicity are potentially serious consequences of stem cell therapy (294). More specifically, to date there have been at least 28 kinds of adverse effects reported (293). Some side effects reported are likely secondary to the delivery procedures rather than the cells (294).…”

Current Spinal Cord Injury Animal Models are Too Simplistic for Clinical Translation

“…As most clinical trials do not discriminate between spinal levels of injuries in patient recruitment, it is important to consider the differences in motor, autonomic and cardiovascular roles of the cervical and thoracic spinal cord. Notably, the thoracic spinal level has comparatively scarce grey matter and the presence of the sympathetic preganglionic neurones within the intermediate lateral horn of the grey matter [35][36][37]. Therefore, it is important to consider the inclusion of cervical level injury in preclinical animal studies.…”