0976 - Influence of Adipose-Derived Regenerative Cells for the Treatment of Knee Osteoarthritis

INTRODUCTION: Adipose-derived regenerative cells (ADRCs) have multilineage potential equivalent to bone marrow-derived stem cells. ADRCs also contains several types of stem and regenerative cells, including Adipose-derived mesenchymal stem cells (ADSCs), vessel-forming cells such as endothelial and smooth muscle cells and their progenitors, and preadipocytes. Because ADRCs can be easily isolated in large amounts from autologous adipose tissue and used without culturing or differentiation induction, ADRCs offer great potential applications in regenerative medicine. There are some reports about effectiveness of ADRCs in orthopaedic animal study. However, there is no report on the clinical outcome of ADRCs for osteoarthritis (OA) of the knee. Therefore, the purpose of this study is to investigate the short-term treatment effect of intra-articular injection of ADRCs on OA of the knee.METHODS: We included 57 patients with varus osteoarthritis of the knee (41 females, and 16 males) who were treated with intra-articular injection of ADRCs between 2016 Nov and 2017 Dec, and were followed-up for 6 months or longer. The mean age at surgery was 69.4 u00b1 6.9 years, the mean follow-up period was 6.0 u00b1 3.0 months and the mean body mass index was 25.1 u00b1 3.1 kg/m2. The patients were divided by Kellgren-Laurence classification as follows; grade I was 0 patient, grade II was 11 patients, grade III was 36 patients and grade IV was 10 patients. The Celutionu00aeufe0e 800/CRS system was used in this study to extract ADRCs from the patientsu2019 abdominal or breech subcutaneous fat. Patients received an intra-articular injection of 5.0u00d7107 cells of ADRCs into the knee. The mean ADRCs viability was 90.6% u00b1 2.7%. Clinical evaluations were performed with range of motion (ROM) of the knee, muscle force of extension and flexion of the knee using hand-held dynamometer, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS) for pain (0-100), the Japanese Knee Osteoarthritis Measure (JKOM) and the Knee injury and Osteoarthritis Outcome Score (KOOS). Structural evaluations were also performed with Femoro-tibial angle (FTA) using radiograph, T2 mapping value using magnetic resonance imaging (MRI) and some parts of MRI Osteoarthritis Knee Score (MOAKS) 5: bone marrow resions (BML) score, articular cartilage score, osteophytes score and Hoffa-effusion synovitis score. The method of calculating T2 mapping value was showed in Fig. 1. These clinical and structural evaluations were performed preoperatively, 1-month, 3-month and 6-month postoperatively, and compared among the 4 time periods using repeated measures analysis of variance. P<0.05 was considered statistically significant.RESULTS: Regarding clinical evaluations, the mean ROM was -6.8u00b0u2013131.6u00b0, -5.6u00b0-132.7u00b0, -5.2u00b0-134.8u00b0 and -4.5u00b0-134.9 u00b0 preoperatively, 1-month, 3-month and 6-month postoperatively, respectively. The mean extension of the knee 6-month postoperatively was significantly better than preoperatively. Muscle force of extension and flexion of the knee were 197.3 and 92.5, 192.8 and 99.5, 211.4 and 110.2, and 299.3 and 120.0, preoperatively, 1-month, 3-month and 6-month postoperatively, respectively. The mean muscle force of flexion of the knee 3-month and 6-month postoperatively was significantly better than preoperatively. The mean total score of VAS and KOOS 1-month, 3-month and 6-month postoperatively were significantly better than preoperatively. Furthermore, the mean total score of WOMAC and JKOM was 3-month and 6-month postoperatively were significantly better than preoperatively. Regarding structural evaluations, the mean FTA was 182.8, 182.9, 182.7 and 182.6 preoperatively, 1-month, 3-month and 6-month postoperatively, respectively. There was no significant difference in the mean FTA among 4 time periods. The mean T2 mapping values of lateral tibia in central and anterior area 6-month postoperatively were significantly higher than preoperatively. Furthermore, the mean T2 mapping value of medial tibia in anterior area 6-month postoperatively was significantly higher than preoperatively. BML and Hoffa-effusion synovitis scores 3-month postoperatively were significantly better than preoperatively.DISCUSSION: The current study reported the first clinical outcome of the intra-articular injection of ADRCs into the knee joint. The short-term clinical evaluation of intra-articular injection of ADRCs on OA of the knee was excellent. Regarding structural evaluation, the intra-articular injection of ADRCs tended to suppress inflammatory changes in the joint of the knee, but obvious cartilare regeneration was not observed. Further study including in vitro study was considered necessary in the future.SIGNIFICANCE: We suggest that when we think about treating patients with OA of the knee, the method of intra-articular injection of ADRCs into the knee joint can be an innovative approach.

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