Allogeneic stem cell strategies in bone regeneration: A systematic review and meta-analysis

Autologous mesenchymal stem cells (MSC) are widely regarded as the gold standard for stem cell-based bone regenerative applications due to their strong osteogenic potential. This systematic review with meta-analysis aims to evaluate existing evidence on the use of allogeneic MSC as an alternative, comparing their regenerative efficacy, immunological response, and clinical outcomes to autologous MSC, including their performance when combined with various biomaterial scaffolds. Based on the objective requirements and inclusion criteria, an initial search was conducted in two databases, Medline and Embase. Review articles were excluded, leaving only individual studies. These were manually evaluated, first by assessing the title and abstract before conducting a full review of the remaining articles. Compliance with the ARRIVE guidelines was evaluated for quality assessment. Thirteen studies met the inclusion criteria, comprising various animal models and one human study. Overall, bone regeneration outcomes were comparable between autologous and allogeneic MSC. Quantitative analyses (micro-computed tomography (µCT), radiography, histology) showed similar bone volume and mineralization across groups, with some studies reporting slightly higher values for autologous MSC. The meta-analysis of nine studies revealed a small effect favoring autologous MSC, however not statistically significant (Hedges' g = 0.26; 95% CI: 0.04-0.56), with low heterogeneity (I² = 11.4%). Allogeneic MSC induced only transient or mild immune responses without impairing bone healing. Findings from the included human trial supported preclinical evidence, indicating that allogeneic MSC are safe and feasible for clinical application. The potential for using allogeneic instead of autologous MSC appears promising. Overall, the literature indicates no substantial differences between the use of allogeneic and autologous MSC. Lack of standardization of data underscores the need for further research. Additional human studies are needed to validate the results obtained from animal studies.