Nerve gaps repaired with acellular nerve allografts recellularized with Schwann-like cells: Preclinical trial.

BACKGROUND: Acellular nerve allografts (ANA) recellularized with mesenchymal stem cells (MSC) or Schwann cells (SC) are, at present, a therapeutic option for peripheral nerve injuries (PNI). This study aimed to evaluate the regenerative and functional capacity of a recellularized allograft (RA) compared with autograft nerve reconstruction in PNI. METHODS: Fourteen ovines were randomly included in two groups (n=7). A peroneal nerve gap 30 mm in length was excised, and nerve repair was performed by the transplantation of either an autograft or a recellularized allograft with SC-like cells. Evaluations included a histomorphological analysis of the ANA, MSC pre differentiated into SC-like cells, at one year follow-up functional limb recovery (support and gait), and nerve regeneration using neurophysiological tests and histomorphometric analysis. All evaluations were compared with the contralateral hindlimb as the control. RESULTS: The nerve allograft was successfully decellularized and more than 70% of MSC were pre differentiated into SC-like cells. Functional assessment in both treated groups improved similarly over time (p <0.05). Neurophysiological results (latency, amplitude, and conduction velocity) also improved in both treated groups at twelve months. Histological results demonstrated a less organized arrangement of nerve fibers (p <0.05) with an active remyelination process (p <0.05) in both treated groups compared with controls at twelve months. CONCLUSIONS: ANA recellularized with SC-like cells proved to be a successful treatment for nerve gaps. Motor recovery and nerve regeneration were satisfactorily achieved in both graft groups compared with their contralateral nontreated nerves. This approach could be useful for the clinical therapy of PNI.

Cotransfected human chondrocytes: over-expression of IGF-I and SOX9 enhances the synthesis of cartilage matrix components collagen-II and glycosaminoglycans

Damage to cartilage causes a loss of type II collagen (Col-II) and glycosaminoglycans (GAG). To restore the original cartilage architecture, cell factors that stimulate Col-II and GAG production are needed. Insulin-like growth factor I (IGF-I) and transcription factor SOX9are essential for the synthesis of cartilage matrix, chondrocyte proliferation, and phenotype maintenance. We evaluated the combined effect of IGF-I and SOX9 transgene expression on Col-II and GAG production by cultured human articular chondrocytes. Transient transfection and cotransfection were performed using two mammalian expression plasmids (pCMV-SPORT6), one for each transgene. At day 9 post-transfection, the chondrocytes that were over-expressing IGF-I/SOX9 showed 2-fold increased mRNA expression of the Col-II gene, as well as a 57% increase in Col-II protein, whereas type I collagen expression (Col-I) was decreased by 59.3% compared with controls. The production of GAG by these cells increased significantly compared with the controls at day 9 (3.3- vs 1.8-times, an increase of almost 83%). Thus, IGF-I/SOX9 cotransfected chondrocytes may be useful for cell-based articular cartilage therapies.

Cotransfected human chondrocytes: over-expression of IGF-I and SOX9 enhances the synthesis of cartilage matrix components collagen-II and glycosaminoglycans.

Damage to cartilage causes a loss of type II collagen (Col-II) and glycosaminoglycans (GAG). To restore the original cartilage architecture, cell factors that stimulate Col-II and GAG production are needed. Insulin-like growth factor I (IGF-I) and transcription factor SOX9are essential for the synthesis of cartilage matrix, chondrocyte proliferation, and phenotype maintenance. We evaluated the combined effect of IGF-I and SOX9 transgene expression on Col-II and GAG production by cultured human articular chondrocytes. Transient transfection and cotransfection were performed using two mammalian expression plasmids (pCMV-SPORT6), one for each transgene. At day 9 post-transfection, the chondrocytes that were over-expressing IGF-I/SOX9 showed 2-fold increased mRNA expression of the Col-II gene, as well as a 57% increase in Col-II protein, whereas type I collagen expression (Col-I) was decreased by 59.3% compared with controls. The production of GAG by these cells increased significantly compared with the controls at day 9 (3.3- vs 1.8-times, an increase of almost 83%). Thus, IGF-I/SOX9 cotransfected chondrocytes may be useful for cell-based articular cartilage therapies.