Cell Cotransplantation Strategies for Vascularized Craniofacial Bone Tissue Engineering: A Systematic Review and Meta-Analysis of Preclinical In Vivo Studies.

Relatively higher-quality human studies compared with other topics in this database, e.g. multiple RCTs or systematic reviews. This does not mean it is standard or approved care.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The regenerative potential of tissue-engineered bone constructs may be enhanced by in vitro coculture and in vivo cotransplantation of vasculogenic and osteogenic (progenitor) cells. The objective of this study was to systematically review the literature to answer the focused question: In animal models, does cotransplantation of osteogenic and vasculogenic cells enhance bone regeneration in craniofacial defects, compared with solely osteogenic cell-seeded constructs? Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, electronic databases were searched for controlled animal studies reporting cotransplantation of endothelial cells (ECs) with mesenchymal stem cells (MSCs) or osteoblasts in craniofacial critical size defect (CSD) models. Twenty-two studies were included comparing outcomes of MSC/scaffold versus MSC+EC/scaffold (co)transplantation in calvarial (n = 15) or alveolar (n = 7) CSDs of small (rodents, rabbits) and large animal (minipigs, dogs) models. On average, studies presented with an unclear to high risk of bias. MSCs were derived from autologous, allogeneic, xenogeneic, or human (bone marrow, adipose tissue, periosteum) sources; in six studies, ECs were derived from MSCs by endothelial differentiation. In most studies, MSCs and ECs were cocultured in vitro (2-17 days) before implantation. Coculture enhanced MSC osteogen

Evidence level

Relatively higher-quality human studies compared with other topics in this database, e.g. multiple RCTs or systematic reviews. This does not mean it is standard or approved care.

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