Incomplete Eradication of Persistent Infection May Impede Union: Our Experience in Treating Fracture Non-Unions with Allogenic MSC

Abstract

Introduction : Non-union remains a major clinical challenge for orthopaedic surgeons, as the treatments are associated with risks for complications, and sometimes multiple surgeries are required. Mesenchymal stem cells (MSCs) have been found to aid in osteogenesis and fracture healing; however, the number of studies on MSC application for treating non-unions is still sparse. We present a translational study of 8 subjects treated with MSC implantation, along with those considered as standard treatments in treating non-unions. To our knowledge, this is the most extensive clinical study on the use of MSCs to treat fracture non-unions. Methods: We performed 20x10 6 units of MSC implantations derived from adipose tissue, bone marrow, and umbilical cord on subjects diagnosed with fracture non-union of the long bone, along with internal fixation and hydroxyapatite-calcium sulphate (HA-CaSO 4 ) pellets. We excluded pathological fractures, subjects with immunological deficiencies (type II diabetes mellitus, and HIV/AIDS), and subjects with a history of immunosuppressive therapies. All subjects were assessed using the Disabilities of the Arm, Shoulder, and Hand (DASH) or Lower Extremities Functional Scale (LEFS), and visual analog score (VAS). Serial radiological images were also assessed using Tiedeman and Lane-Sandhu scoring to determine union. Follow up assessments were performed every three months for at least 12 months or until clinical and radiological union was achieved. Results: Four (50%) out of eight subjects developed union in a median of five (3-12) months. There was a reduction of VAS, from a median of 1 (0-6) to 0 (0-4), and an increase in mean LEFS/DASH of 56.25 ± 10.71 to 65 ± 22.72. However, the infection was identified in 3 (37.5%) subjects. Methicillin-resistant Staphylococcus aureus (MRSA) was identified in two (25%) subjects, while one was infected with Escherichia coli . No other adverse events occurred during the follow-up period. Conclusion: Allogenic MSC implantation can be used as a potential and safe therapy for fracture non-union. However, the presence of infection may interfere with bone healing; thus, thorough eradication of infection must be ensured to achieve fracture union. Further clinical studies are required to investigate the safety and efficacy of allogeneic MSC implantation.