Efficacy of adipose tissue-derived stem cells in locomotion recovery after spinal cord injury: a systematic review and meta-analysis on animal studies

Abstract

Background Considerable disparities exist on the use of adipose tissue-derived stem cells (ADSCs) for treatment of spinal cord injury (SCI). Hence, the current systematic review aimed to investigate the efficacy of ADSCs in locomotion recovery following SCI in animal models. Methods A search was conducted in electronic databases of MEDLINE, Embase, Scopus, and Web of Science until the end of July 2019. Reference and citation tracking and searching Google and Google Scholar search engines were performed to achieve more studies. Animal studies conducted on rats having SCI which were treated with ADSCs were included in the study. Exclusion criteria were lacking a non-treated control group, not evaluating locomotion, non-rat studies, not reporting the number of transplanted cells, not reporting isolation and preparation methods of stem cells, review articles, combination therapy, use of genetically modified ADSCs, use of induced pluripotent ADSCs, and human trials. Risk of bias was assessed using Hasannejad et al.’s proposed method for quality control of SCI-animal studies. Data were analyzed in STATA 14.0 software, and based on a random effect model, pooled standardized mean difference with a 95% confidence interval was presented. Results Of 588 non-duplicated papers, data from 18 articles were included. Overall risk of bias was high risk in 8 studies, some concern in 9 studies and low risk in 1 study. Current evidence demonstrated that ADSCs transplantation could improve locomotion following SCI (standardized mean difference = 1.71; 95%CI 1.29–2.13; p < 0.0001). A considerable heterogeneity was observed between the studies (I2 = 72.0%; p < 0.0001). Subgroup analysis and meta-regression revealed that most of the factors like injury model, the severity of SCI, treatment phase, injury location, and number of transplanted cells did not have a significant effect on the efficacy of ADSCs in improving locomotion following SCI (pfor odds ratios > 0.05). Conclusion We conclude that any number of ADSCs by any prescription routes can improve locomotion recovery in an SCI animal model, at any phase of SCI, with any severity. Given the remarkable bias about blinding, clinical translation of the present results is tough, because in addition to the complexity of the nervous system and the involvement of far more complex motor circuits in the human, blinding compliance and motor outcome assessment tests in animal studies and clinical trials are significantly different.

Ameliorative potential of stem cells from human exfoliated deciduous teeth (SHED) in preclinical studies: A meta-analysis

“…Furthermore, the mode of delivery and the form of SHED in the included studies were similar, while the follow-up period in two studies [ 21 , 22 ] was eight and seven weeks, respectively, and subsequently significantly altered the controls. Concurrent to our investigation, the impending role of MSCs in animal models and clinical trials depicted significant improvement in ASIA motor score, sensory score, and locomotion [ [52] , [53] , [54] ]. Similar to SCI, treatment of MSCs in PD, AD, FCI, and PNI illustrated a significantly positive effect.…”

Effects of melatonin-pretreated adipose-derived mesenchymal stem cells (MSC) in an animal model of spinal cord injury

“…Further studies are warranted to shed light on the effect of different concentrations of melatonin as well as stem cell types on neuronal differentiation. The ability of ADSCs to differentiate into motor neurons, along with their anti-inflammatory and anti-apoptotic capabilities, make these cells an ideal candidate for mitigating disabilities following SCI [ 30 ]. Given that in SCI, loss of mobility is a main cause of disability, replacement of lost motor neuron cells and prevention of secondary damage to the remaining neuron cells can play a crucial role in improving a person's motor function [ 27 ].…”

“…Given that in SCI, loss of mobility is a main cause of disability, replacement of lost motor neuron cells and prevention of secondary damage to the remaining neuron cells can play a crucial role in improving a person's motor function [ 27 ]. A systematic review by Rafiei et al also demonstrated that ADSC is able to improve the performance of motor tests, especially the Basso, Beattie, Bresnahan (BBB), irrespective of the type, severity, and place of injury, type of injection, and the number of injected cells [ 30 ]. In the present study, the results of the BBB test exhibited that eight weeks after transplantation, the motor function of the models improved significantly.…”

Exploring the therapeutic potential of Sirt6-enriched adipose stem cell-derived exosomes in myocardial ischemia–reperfusion injury: unfolding new epigenetic frontiers

“…These rats were chosen specifically for this study and their use was permitted by the Ethics Review Committee of Animal Experimentation of Guizhou Medical University, under approval number AEEIF2200612. The process of ASC acquisition and preparation began with the isolation of rat adipose tissues [ 21 , 22 ]. Following rat euthanasia under ethically approved protocols, adipose tissues were collected, processed, and subjected to a series of enzymatic digestion and centrifugation steps to separate the stromal vascular fraction, which contains the ASCs.…”