Autologous Stem Cell Therapy for Fracture Non-union Healing

Study Overview
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Brief Summary
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Do mesenchymal stem cells accelerate new bone formation in persistent non-unions.

Detailed Description
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Do mesenchymal stem cells accelerate new bone formation in persistent non-unions treated with carrier plus in vitro expanded autologous BMSCs or carrier alone (control). Secondary aims were to analyze predictors of union in these patients and describe adverse events at final follow-up.

Official Title
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Autologous Stem Cell Therapy for Fracture Non-union Healing

Conditions
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Non-union of Fractures

Intervention / Treatment
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* Biological: carrier plus in vitro expanded autologous BMSCs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An established non-union according to the US Food & Drug Administration criteria14. Non-union following fracture of tibia or femur suitable for synthetic bone grafting. Exclusion Criteria: Skeletal immaturity. Pregnant or breast-feeding. Non-union following pathological fractures. Positive to Hepatitis B, Hepatitis-C or HIV. Infection during BMSC culture.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 76 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: carrier plus BMSCs<br>carrier plus in vitro expanded autologous BMSCs | Biological: carrier plus in vitro expanded autologous BMSCs<br>* The non-unions of fractures were stabilized with internal or external fixation devices. The non-union site was clearly exposed and decorticated to introduce sub-periosteal bone graft. Depending on the surgical approach, the site was partitioned in either medial/lateral or anterior/posterior sides. The contents of each universal container were mixed individually with a carrier by the surgeon, who was blinded to the contents of the container<br>|
| Placebo Comparator: carrier alone (control).<br>Carrier alone | Biological: carrier plus in vitro expanded autologous BMSCs<br>* The non-unions of fractures were stabilized with internal or external fixation devices. The non-union site was clearly exposed and decorticated to introduce sub-periosteal bone graft. Depending on the surgical approach, the site was partitioned in either medial/lateral or anterior/posterior sides. The contents of each universal container were mixed individually with a carrier by the surgeon, who was blinded to the contents of the container<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiological assessment of new callus and fracture bridging | The primary outcome measure was formation of new callus and cortical bridging, assessed from pre-operative and multiple post-operative radiographs and CT-scans up to 12 months. These images were divided into early (0-3 months) and late (9-12 months) groups. Non-unions were assessed from anonymized slides by four independent reviewers (two radiologists and two orthopedic surgeons) blinded to the side of cell insertion. Each slide had a pre-operative radiograph for comparison but no indication of time since surgery, and showed a medial/ lateral or an anterior/ posterior view depending on the surgical approach . At first, each reviewer indicated the side with largest callus and most cortical bridging pre-operatively. Then each reviewer examined subsequent radiographs to indicate the side with the largest increase in new callus and cortical bridging. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EQ-5D | Change in EQ-5D index at 1 year was used as secondary outcome measures. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-union, fracture, bone marrow stem cells