Abstract
Distraction osteogenesis (DO) relies on the recruitment and proliferation of mesenchymal stem cells (MSC) to the target site, where they differentiate into osteoblasts to promote bone formation. Nevertheless, MSC recruitment appears to be slow and limits bone formation in DO defects. Thus, this systematic review aims to evaluate the ability of locally applied MSC to enhance bone formation in DO preclinical models. Databases were searched for quantitative pre-clinical controlled studies that evaluated the effect of local administration of MSC on DO bone formation. Eligible studies were identified and data regarding study characteristics, outcome measures and quality were extracted. Nine studies met the inclusion criteria. Autogenous and xenogenous MSC were used to promote DO bone formation. These included bone marrow-derived MSC, adipose tissue-derived MSC and MSC derived from human exfoliated deciduous teeth. Meta-analysis was not possible due to heterogeneities in study designs. Local MSC implantation was not associated with adverse effects. In 4 out of the 5 studies, locally delivered undifferentiated bone-marrow MSC had a positive effect on DO bone formation. Few studies evaluated the therapeutic effects of MSC from other sources. The adjunct use of biologically active molecules or forced expression of key genes involved in osteogenesis further boosted the ability of bone-marrow MSC to promote DO bone formation. While risk of bias and heterogeneity limited the strength of this systematic review, our results suggest that the use of MSC is safe and may provide beneficial effects on DO bone formation.
Highlights
Distraction osteogenesis (DO) is a method that induces osseous neoformation between two bone segments surgically separated in response to the application of graduated and controlled traction force throughout the bony gap.[1,2] This technique have been used in treatment of congenital and acquired craniofacial deformations, as it provides some advantages over traditional autogenic bone grafts, including no need for a second surgical site, reduced operating time and post-operativeBraz
DO relies on the recruitment and proliferation of mesenchymal stem cells (MSC) to the target site, where they differentiate into osteoblasts to promote bone formation/mineralization.[5]
Results from this study showed that osteogenically differentiated bone marrow-derived MSC (BM-MSC) arranged in cell sheets promoted greater bone formation and remodeling into mature cortical bone, than undifferentiated BM-MSC sheets and negative control treatment.[8]
Summary
Distraction osteogenesis (DO) is a method that induces osseous neoformation between two bone segments surgically separated in response to the application of graduated and controlled traction force throughout the bony gap.[1,2] This technique have been used in treatment of congenital and acquired craniofacial deformations, as it provides some advantages over traditional autogenic bone grafts, including no need for a second surgical site, reduced operating time and post-operativeBraz. Distraction osteogenesis (DO) is a method that induces osseous neoformation between two bone segments surgically separated in response to the application of graduated and controlled traction force throughout the bony gap.[1,2] This technique have been used in treatment of congenital and acquired craniofacial deformations, as it provides some advantages over traditional autogenic bone grafts, including no need for a second surgical site, reduced operating time and post-operative. DO relies on the recruitment and proliferation of mesenchymal stem cells (MSC) to the target site, where they differentiate into osteoblasts to promote bone formation/mineralization.[5] MSC recruitment into DO defects is stimulated endogenously by the fracture healing process and exogenously by mechanical distraction.[6] under standard circumstances, MSC recruitment appears to be slow and limits the amount of DO bone formation.[7] MSC migration may be further compromised in elderly and under conditions such as poor vascularity, severe trauma and radiotherapy. DO animal models were developed to evaluate the effect of locally applied MSC on DO bone formation.[8,9,10,11,12,13,14,15,16] this systematic review aims to evaluate the following PICO question: “In animals submitted to DO (Participant), how does local MSC administration (Intervention), compared to no MSC administration (Comparison), influence bone consolidation (Outcome)?”
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