Neuronal Differentiation of Human Adipose Tissue–Derived Stem Cells for Peripheral Nerve Regeneration In Vivo

Abstract

To evaluate the ability of a tissue-engineered nerve construct composed of a nerve guidance channel and neurally differentiated human adipose tissue-derived stem cells (hASCs) to enhance peripheral nerve regeneration in a rat sciatic nerve model. A 13-mm sciatic nerve gap was bridged with silastic conduits in 64 athymic nude rats, and differentiated hASCs were implanted into the nerve gap. The effect of repetitive renewal of differentiation medium on days 14 and 28 was further tested. Adequate negative controls and isograft controls were used. Academic research. The hASCs were isolated from human adipose tissue of patients undergoing liposuction procedures. Direct measurements of nerve function included sciatic functional index score, extensor postural thrust, and sensory evaluation. Indirect measurements included gastrocnemius and soleus muscle atrophy. Histomorphometric evaluation included the number and diameter of axons and fibers, nerve fiber density, myelin thickness, g-ratio (axon diameter-total fiber diameter ratio), and myelin thickness-axon diameter ratio. The use of hASCs demonstrated significantly improved functional recovery as measured by the sciatic functional index, extensor postural thrust, sensory evaluation, and gastrocnemius and soleus muscle weight after 14 days and 1, 2, 3, and 4 months. Groups with their medium renewed also demonstrated further enhanced functional recovery compared with their counterparts that did not have their medium renewed. This tissue-engineered nerve construct using hASCs was able to improve functional recovery during the first 4 months, comparable with nerve isografts.