gms | German Medical Science

Objectives: The use of stem cell-based therapies for musculoskeletal injuries is a rapidly evolving field of research globally and becoming a more commonly explored option for clinical application in orthopedic surgery. While prior studies on allograft stem cell products have demonstrated varying levels of success in musculoskeletal tissue regeneration and healing, there remains a lack of data regarding safety of these products. This study aims to investigate the clinical safety of allograft stem cell products in orthopedic surgeries in the United States of America using a national adverse event reporting database.

Methods: The United States Food and Drug Administration (FDA) MedWatch system is a national surveillance containing information on adverse event reports submitted by healthcare professionals, consumers, and manufacturers. Under the Freedom of Information Act, we requested all adverse event reports submitted to the MedWatch database from 2004 through 2016 for the following four products: Osteocel (NuVasive); Trinity Evolution Matrix and Trinity Elite (Orthofix); AlloStem (AlloSource); and map3 (RTI Surgical). Each case report was retrospectively reviewed and analyzed for the following primary endpoints: number of case reports and unique patients, indication for product usage, type of adverse event, and result of the case investigation.

Results and conclusion: Fifty-one case reports of adverse events that occurred between 2010 and 2016 were received from the FDA MedWatch database for two of the four allograft products. Eighteen of the 51 reports were unique adverse event cases, and these are listed in chronological order in Table 1 [Tab. 1].

There were 11 cases on Osteocel, seven of which were unique patients. There were 40 cases on Trinity Evolution Matrix/Trinity Elite, 11 of which were unique patients. Indications for orthopedic usage were spine and foot surgeries. Types of adverse event listed were post-operative infection, post-operative diagnosis of leukemia and HIV, and pseudoarthrodesis. In all incidents of infection or disease transmission, the case investigation reported that donor serology and sterility test results were negative or nonreactive.

There is currently no definitive evidence in the FDA surveillance database that directly links adverse events to the use of MSC-containing bone allografts in orthopedic procedures in the United States of America. Our study demonstrates a relatively low number of adverse event reports submitted. Furthermore, our study highlights the limitations of current methods available to assess for product safety on a national level. The long-term safety of MSC-containing allografts remains elusive and to be determined through active surveillance and the increased vigilance of physicians, consumers, and manufacturers on a global scale.