Ex vivo bone morphogenetic protein-9 gene therapy using human mesenchymal stem cells induces spinal fusion in rodents

OBJECTIVE: Ex vivo gene therapy with the use of human mesenchymal stem cells (hMSCs) and bone morphogenetic protein (BMP) genes provides a local supply of precursor cells and a supraphysiological dose of osteoinductive molecules that may promote bone formation in patients with inadequate hMSC populations because of age, osteoporosis, metastatic bone disease, iatrogenic depletion, or other metabolic derangements. This study was undertaken to evaluate the efficacy of ex vivo gene therapy with the use of hMSCs and the BMP-9 gene to promote spinal fusion in the rat. METHODS: Sixteen athymic nude rats were treated with hMSCs transduced with recombinant, replication-defective Type 5 adenovirus containing the cytomegalovirus promoter and either the BMP-9 (Ad-BMP-9) or the beta-galactosidase (Ad-beta-gal) gene. Ad-beta-gal served as the control. Each animal received a percutaneous, paraspinal injection of 10(6) hMSCs transduced with 50 plaque-forming units/cell adenovirus in the lumbar region, with Ad-BMP-9 on the left and Ad-beta-gal on the right. At 8 weeks postinjection, computed tomographic scans of the lumbosacral spine were obtained, and the lumbosacral spine specimens were examined histologically. RESULTS: Both computed tomographic studies and histological analysis clearly demonstrated large volumes of ectopic bone at the Ad-BMP-9-transduced hMSC injection sites, resulting in successful spinal fusion and no evidence of nerve root compression or local or systemic toxicity. The contralateral regions that were treated with Ad-beta-gal-transduced hMSCs showed no evidence of osteogenesis. CONCLUSION: The results of this study suggest that hMSC and BMP-9 ex vivo gene therapy may be useful in inducing spinal fusion as well as other related procedures and certainly warrants further clinical development.     

Preclinical management of multiple trauma

Approximately 8000 patients with multiple trauma are admitted annually to an emergency room in Germany. The prognosis of these severely injured patients is influenced in particular by concomitant craniocerebral injury, an abdominal wound, or thoracic trauma. Hypoxia and hypotension subsequent to shock induced by hemorrhagic-traumatic effects are of prime importance. Preclinical management thus includes examining the injured patient, immobilizing the spine, ensuring airway patency, stabilizing cardiovascular status suitting the approach to the injury pattern, commensurate care of partial injuries, pain therapy, as well as rapid and careful transportation to the nearest qualified trauma center. Management of patients with multiple trauma poses a particular challenge to the responding team. This article in the continuing education series deals with current algorithms for preclinical management of patients with multiple injuries with particular focus on the significant factor of time.     

Inzidenz schwerer Verletzungen

It is still unknown exactly how many persons sustain a severe injury (ISS > or =16) in Germany each year. Considering the growing restrictions and the introduction of DRGs, it was necessary to acquire data about this rather resource-intensive aspect of trauma care. The aim of this study was therefore to assess the incidence of severe trauma within a defined population. In a retrospective study all surgical emergencies within a 5-year period (1996-2000) were reviewed. Data on type, pattern, severity of injury, and mortality were extracted from the patients' records. During the study period 454 persons sustained a severe injury (ISS > or =16), 112 individuals died at the scene of the accident, and 64 during the hospital stay. The average ISS of the surviving patients was 27 (ISS 16-75). The calculated incidence of severe trauma was 25/100,000 inhabitants per year. Extrapolated, up to 40,000 persons sustain a severe injury each year in Germany. For the first time, this study has provided data on the incidence of major trauma in Germany. Based on the acquired data and a previous cost analysis, hospital treatment costs for severely injured patients amount to up to 2 billion Euros per year in Germany.