A Systematic Review of Bone Marrow Stromal Cells and Periosteum-Derived Cells for Bone Regeneration

Bone marrow stromal cells (BMSCs) and periosteum-derived cells (PDCs) represent promising skeletal stem cell sources to treat critical-size bone defects. However, the large number of preclinical tests with a variety of in vivo data complicates the selection of cells for further clinical translation. This systematic review aims to analyze the in vivo bone-forming efficacy of BMSCs- and PDCs-based approaches in all published preclinical experiments until November 2020. For this purpose, four databases (PubMed, Embase, Cochrane Central Register of Controlled Trial, and Web of Science) were searched for eligible literature, which yielded a total of 94 full-text articles for systematic review. This review generated an evidence-based list of BMSC- or PDC-based approaches, which have been evaluated for bone formation in different animal models. Among them, 74 studies were included for pairwise and network meta-analysis. The results revealed that both PDC and BMSC had beneficial bone-forming efficacy compared to bare scaffold. In addition, BMSC- and PDC-based approaches had no significant difference regarding in vivo bone-forming efficacy. However, BMSC-based approach had a higher probability to be ranked better than PDC-based approach. Furthermore, the review discusses (i) the possible risk of bias of the in vivo evaluation of cell-based approaches, (ii) the difficulty in replication of such experiments due to frequent poor reporting of the methods and results, and (iii) the clinical relevance of the currently utilized BMSC- and PDC-based approaches. Systematic review registration: The study was prospectively registered in PROSPERO, Registration No. CRD42021270922.