Response to: cytokine profile of autologous conditioned serum for treatment of osteoarthritis, in vitro effects on cartilage metabolism and intra-articular levels after injection - authors' reply

Abstract

We thank Moser for his comments [1] on the paper [2] we published in a previous issue of Arthritis Research & Th erapy. To dispel any concerns about the proper use of the product, the autologous conditioned serum (ACS) in this study was prepared in a GMP (good manufacturing practice) facility in strict accordance with the guidelines supplied by the manufacturer (Orthogen, Dusseldorf, Germany) and was injected six times at 3-day intervals in accordance with the instructions given. As recommended, immediately before injection of ACS, synovial fl uid was carefully aspirated to minimize ACS dilution. Th is synovial fl uid was used to determine the cytokine levels before and during ACS treatment. We showed that, 3 days after injection, cytokine levels were at baseline and had no secondary eff ects on other cyto kines. Th is fi nding is not in confl ict with that of Darabos and colleagues [3], whose publication is cited by Moser; upon careful reading of that publication, none of the eff ects of ACS injection, including the alleged decrease in synovial fl uid levels of interleukin-1 (IL-1), turned out to be statistically signifi cant. We certainly agree with Moser that in vitro and in vivo studies should be well controlled. However, in the case of ACS, the use of an autologous product is not required; this autologous product is devoid of cells, which are the only factors capable of evoking an immune response upon transfer of human materials to human recipients. We have used unconditioned serum as controls in our in vitro studies because serum in general seems to be more amenable to cartilage health than either saline or the synovial fl uid the tissue is exposed to in vivo [4]. In this setup, we could not demonstrate any eff ect of conditioning the serum. Th e observation that IL-1 and tumor necrosis factor-alpha levels were upregulated in ACS, in contrast to the levels found previously upon characterization of ACS, may be due to the use of healthy subjects in the latter case, whereas we characterized the ACS prepared from osteoarthritis (OA) patients, the intended target population. Blood from OA patients was recently