Objectives

Traumatic brachial plexus injury causes severe functional impairment of the arm. Elbow flexion is often affected. Nerve surgery or tendon transfers provide the only means to obtain improved elbow flexion. Unfortunately, the functionality of the arm often remains insufficient. Stem cell therapy could potentially improve muscle strength and avoid muscle-tendon transfer. This pilot study assesses the safety and regenerative potential of autologous bone marrow-derived mononuclear cell injection in partially denervated biceps.

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 < 0.001) and a decrease of 51% in fibrosis (P = 0.012). Histological changes were most apparent in group B with an increase of 126% in myofiber diameter (P = 0.019), 100% in capillary to myofiber ratio (P = 0.027), and a decrease of 70% in fibrosis (P = 0.023). EMG demonstrated an increase of 36% in amplitude (P = 0.045), 29% in duration (P = 0.005) and 29% in number of phases of the motor unit potentials (P = 0.002). CT-scan analysis showed a decrease of 48% in mean muscle density (P = 0.009).

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.