Combined meta-analysis of preclinical cell therapy studies shows overlapping effect modifiers for multiple diseases
Open Access
- 19 April 2021
- journal article
- review article
- Published by Portico in BMJ Open Science
- Vol. 5 (1), e100061
- https://doi.org/10.1136/bmjos-2020-100061
Abstract
Introduction Cell therapy has been studied in many different research domains. Cellular replacement of damaged solid tissues is at an early stage of development, with much still to be understood. Systematic reviews and meta-analyses are widely used to aggregate data and find important patterns of results within research domains. We set out to find common biological denominators affecting efficacy in preclinical cell therapy studies for renal, neurological and cardiac disease. Methods We used datasets of five previously published meta-analyses investigating cell therapy in preclinical models of chronic kidney disease, spinal cord injury, stroke and ischaemic heart disease. We transformed primary outcomes to ratios of means to permit direct comparison across disease areas. Prespecified variables of interest were species, immunosuppression, cell type, cell origin, dose, delivery and timing of the cell therapy. Results The five datasets from 506 publications yielded data from 13 638 animals. Animal size affects therapeutic efficacy in an inverse manner. Cell type influenced efficacy in multiple datasets differently, with no clear trend for specific cell types being superior. Immunosuppression showed a negative effect in spinal cord injury and a positive effect in cardiac ischaemic models. There was a dose–dependent relationship across the different models. Pretreatment seems to be superior compared with administration after the onset of disease. Conclusions Preclinical cell therapy studies are affected by multiple variables, including species, immunosuppression, dose and treatment timing. These data are important when designing preclinical studies before commencing clinical trials.Keywords
This publication has 32 references indexed in Scilit:
- Human Blood and Cardiac Stem Cells Synergize to Enhance Cardiac Repair When Cotransplanted Into Ischemic MyocardiumJournal of the American College of Cardiology, 2013
- Large animal models for stem cell therapyStem Cell Research & Therapy, 2013
- Enhanced Effect of Combining Human Cardiac Stem Cells and Bone Marrow Mesenchymal Stem Cells to Reduce Infarct Size and to Restore Cardiac Function After Myocardial InfarctionJournal of the American College of Cardiology, 2013
- Stem Cell-Based Therapy for Experimental Stroke: A Systematic Review and Meta-AnalysisInternational Journal of Stroke, 2012
- Safety and Efficacy of Allogeneic Cell Therapy in Infarcted Rats Transplanted With Mismatched Cardiosphere-Derived CellsJournal of the American College of Cardiology, 2012
- Cell Transplantation for Articular Cartilage Defects: Principles of Past, Present, and Future PracticeCell Transplantation, 2011
- Stem cell paracrine actions and tissue regenerationRegenerative Medicine, 2010
- A New Direction for Cardiac Regeneration TherapyCirculation: Heart Failure, 2009
- The ratio of means method as an alternative to mean differences for analyzing continuous outcome variables in meta-analysis: A simulation studyBMC Medical Research Methodology, 2008
- Controlling the risk of spurious findings from meta‐regressionStatistics in Medicine, 2004