Clinical Safety and Effectiveness of Adipose-Derived Stromal Cell vs Stromal Vascular Fraction Injection for Treatment of Knee Osteoarthritis: 2-Year Results of Parallel Single-Arm Trials.

BACKGROUND: There are currently no disease-modifying treatments available for knee osteoarthritis (OA), although cultured adipose-derived stromal cells (ASCs) have shown promise in experimental models. However, given the regulatory limits on the use of cultured cells in humans, previous trials have focused primarily on the stromal vascular fraction (SVF) intra-articular injection. Therefore, the therapeutic value of ASCs for knee OA remains unknown. PURPOSE: To study ASC versus SVF intra-articular injection in patients with Kellgren-Lawrence (KL) knee OA grades 2 to 4 in parallel single-arm trials. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 80 patients were enrolled, with 42 (72 knees) receiving ASC intra-articular injection and 38 (69 knees) receiving SVF. Patient-reported outcome measures were assessed at 1, 3, 6, 12, and 24 months using the Knee injury and Osteoarthritis Outcome Score 5 (KOOS5) and pain visual analog scale (VAS). The percentages of patients achieving the minimal clinically important difference (MCID) and Patient Acceptable Symptom State (PASS) were also calculated. Per protocol, a subset of the ASC group received an ASC booster injection after 6 months. A repeated-measures analysis of variance compared results between treatment arms and by KL grade over time. RESULTS: Patient-reported outcome measures improved substantially after both treatments (P < .05 at all time points), with the ASC group more likely to achieve the MCID (50% vs 24%; P = .01) and PASS (45% vs 24%; P = .04) for the pain VAS and the MCID (43% vs 16%; P = .02) for the KOOS5 at 12 months, although not at 24 months. Knees treated with ASC for KL grade 2/3 OA had significantly superior outcomes compared with those with KL grade 4 OA for the KOOS5 (P = .01) and pain VAS (P = .03), but no such difference was observed in knees treated with SVF. Three patients receiving ASCs (7%; all KL grade 3) sought additional nonoperative treatment by 24 months versus 9 patients receiving SVF (24%; all KL grade 3) (P = .06). ASC booster injections conferred no additional benefit. Notably, patients in the ASC cohort reported more injection-site pain and swelling after the booster injection than after the initial injection (P < .01). CONCLUSION: This represents the first head-to-head comparison of ASCs and SVF for the treatment of knee OA in humans. ASC and SVF injections both substantially improved knee pain and function at all follow-up time points, although ASC injections demonstrated significantly better improvements with regard to the MCID and PASS for the pain VAS and the MCID for the KOOS5 at 12 months. There appears to be no benefit to a booster ASC injection after initial treatment. Given less donor-site morbidity and equivalent superior outcomes at 2 years, the use of ASCs over SVF in the treatment of knee OA may be warranted.

Comparative Clinical Outcomes After Intra-articular Injection With Adipose-Derived Cultured Stem Cells or Noncultured Stromal Vascular Fraction for the Treatment of Knee Osteoarthritis.

BACKGROUND: Intra-articular injection of adipose-derived stem cells (ASCs) has shown promise for improving symptoms and cartilage quality in the treatment of osteoarthritis (OA). However, while most preclinical studies have been performed with plastic-adherent ASCs, most clinical trials are being conducted with the stromal vascular fraction (SVF), prepared from adipose tissue without prior culture. PURPOSE: To directly compare clinical outcomes of intra-articular injection with ASCs or SVF in patients with knee OA. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The authors retrospectively compared 6-month outcomes in 42 patients (59 knees) receiving intra-articular injection with 12.75 million ASCs and 38 patients (69 knees) receiving a 5-mL preparation of SVF. All patients had Kellgren-Lawrence grade 2, 3, or 4 knee OA and had failed standard medical therapy. The visual analog scale (VAS) pain score and Knee injury and Osteoarthritis Outcome Score (KOOS) at baseline and 1, 3, and 6 months after injection were considered as outcomes. Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) criteria were also used to assess positive response. A repeated measures analysis of variance was used for comparison between the treatment groups. RESULTS: No major complications occurred in either group. The SVF group had a higher frequency of knee effusion (SVF 8%, ASC 2%) and minor complications related to the fat harvest site (SVF 34%, ASC 5%). Both groups reported improvements in pain VAS and KOOS domains. Specifically, in the ASC group, symptoms improved earlier (by 3 months; P < .05) and pain VAS decreased to a greater degree (55%; P < .05) compared with the SVF group (44%). The proportion of OMERACT-OARSI responders in the ASC group was slightly higher (ASCs, 61%; SVF, 55%; P = .25). CONCLUSION: It was observed that both ASCs and SVF resulted in clinical improvement in patients with knee OA, but that ASCs outperform SVF in the early reduction of symptoms and pain with less comorbidity.

Clinical results following intra-articular injection of adipose-derived stromal vascular fraction cells in patients with osteoarthritis of the knee.

BACKGROUND: The purpose of this study was to evaluate the clinical results following intra-articular knee injection of Stromal Vascular Fraction (SVF cell therapy). METHODS: This study involved 13 consecutive patients who had received SVF cell therapy at our clinic before November 2015 and completed the 6-month post-treatment follow-up period. For each treatment, approximately 200 mL or more of subcutaneous adipose tissue was harvested using tumescent liposuction technique and manual aspiration of tissue from the lower abdomen using a suction cannula under local anesthesia in the operating room. The adipose tissue harvested was processed using the Celution Centrifuge IV in the cell processing room of our clinic. These cells were injected into the articular cavity of both knees directly. Outcome was assessed on the basis of patient questionnaires using VAS for pain, the Japanese Knee Osteoarthritis Measure (JKOM), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: The 13 patients (26 knee joints), consisting of 2 men and 11 women, had a mean age of 74.5 ± 5.4 years. Eleven patients (9 women, 2 men) presented Grade IV knee OA according to the KL classification. The remaining two patients, both women, had Grade III. Pre-operative scores of JKOM, WOMAC, VAS, and BS-POP (for patients) were 55.9 ± 21.0, 49.6 ± 20.4, 72.7 ± 18.2, and 18.5 ± 2.0. No serious adverse events were reported. One month after injection of SVF, all the scores of JKOM, WOMAC, and VAS were significantly improved over baseline (P < 0.01). Ultimately, the scores were improved by an average of 35% over baseline for JKOM, 32% improvement in WOMAC, and 40% for pain (VAS). CONCLUSIONS: Our approach is unique in that it occurred within the context of the recently enacted Japanese Regenerative Medicine Safety Act which is the first in the world.

Ten years results of bucillamine in the treatment of rheumatoid arthritis.

A 10-year cohort study was performed, involving all of the 118 patients treated with bucillamine in our hospital between 1988 and 1990. Evaluation was made on the basis of erythrocyte sedimentation rate, grip strength, joint score, duration of morning stiffness, and Lansbury index consisting of the above four parameters. Eleven patients were male and 107 were female, with a mean age of 53 years (range: 20-79 years) and a mean duration of illness of 8.2 years (range: 2-31 years). Lansbury index remained significantly suppressed throughout the 10-year period of treatment. Continuous treatment was possible for 10 years in 18 patients (15%: 2 men and 16 women). Stage of disease did not advance in 14 patients. Six patients met the criteria for remission. Of all patients, 50% dropped out of treatment at 2.4 years after the start of treatment and 75% at 5 years. The 100 patients who dropped out could be roughly divided into three groups. One third of them dropped out because of lack of or attenuation of response. Another third dropped out because of referral to other medical facilities or discontinuation of visits to our hospital, and the remaining third dropped out because of adverse reactions to treatment. There was no particular trend in terms of sex, age, duration of sickness, drugs used before bucillamine, or level of activity of rheumatoid arthritis. There were no significant difference in the stage and class of the disease, and other backgrounds between 10-year treatment group and dropout group.