AUTOLOGOUS BONE MARROW TRANSPLANTATION FOR MUSCLE IMPROVEMENT IN TRAUMATIC BRACHIAL PLEXUS INJURIESRESULTS OF A PHASE-1 CLINICAL STUDY

Background: Traumatic brachial plexus (BP) injuries may cause loss of elbow flexion. After nerve surgery active elbow flexion often remains insufficient. Muscle strength improvement via cell therapy would be a potential option and could avoid muscle transfer surgery. The primary objective of this pilot study was to assess the safety and feasibility of autologous bone marrow (BM)-derived mononuclear cell (MNC) injection in partly denervated m. biceps brachii of BP patients. Secondary, this study has focused on the myogenic potential of BM-derived MNC by assessing the morphological and functional improvement of the biceps. Methods: Nine adult BP patients with insufficient force recovery of elbow flexion were included. Three escalating doses (0.9, 4 and 8 * 108) of MNCs were injected in the m. biceps brachii (group A, B and C). In group A, BM was aspirated under local anesthesia (60 ml). In group B and C, BM was aspirated in combination with a muscle tendon transfer (Steindler flexorplasty) under general anesthesia (350 and 650 ml respectively). A muscle biopsy was performed before and 3 months after transplantation. Furthermore, quantitative needle EMG, CT-scan and clinical function was obtained at pre-transplantation and at 3 and 6 months follow-up. The EMG and CT-scan data were blinded during analysis. Results: No negative side effects were observed. Biopsies showed an increase of 80% in myofiber diameter (P = 0.007), 51% in satellite cells (P = 0.045), 83% in capillary to myofiber ratio (P Discussion: This study shows that BM-derived MNC transplantation in a partly denervated muscle of traumatic PB patients is safe and feasible. Muscle improvement was observed in muscle biopsies. Furthermore, changes in EMGs and CT-scans were also suggestive for muscle regeneration. The BM dose applied in group B could represent the optimal dose to enhance partly denervated muscles. The results of the present study require confirmation in a placebo-controlled study.