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
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
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DOI：
10.1177/03635465221107364
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发表时间：
2022-07-14
影响因子：
4.8
通讯作者：
Nakamura, Norimasa
中科院分区：
文献类型：
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作者：
Yokota, Naomasa;Lyman, Stephen;Nakamura, Norimasa
背景：虽然培养的脂肪源性基质细胞（ASCs）在实验模型中显示出前景，但目前还没有可用于膝关节骨关节炎（OA）的疾病改善治疗方法。然而，鉴于在人类中使用培养细胞的监管限制，先前的试验主要集中在基质血管分数（SVF）关节内注射。因此，ASCs对膝关节OA的治疗价值尚不清楚。目的：在平行单臂试验中研究2至4级Kellgren-Lawrence （KL）膝关节OA患者关节内注射ASC与SVF的对比。研究设计：队列研究；证据等级2。方法：共纳入80例患者，其中42例（72膝）接受ASC关节内注射，38例（69膝）接受SVF。采用膝关节损伤和骨关节炎结局评分5 （KOOS5）和疼痛视觉模拟量表（VAS），在1、3、6、12和24个月对患者报告的结果进行评估。同时计算达到最小临床重要差异（MCID）和患者可接受症状状态（PASS）的患者百分比。每个方案，ASC组的一个子集在6个月后接受ASC加强注射。重复测量的方差分析比较了治疗组之间的结果和随时间的KL等级。结果：患者报告的结果测量在两种治疗后都有显著改善（所有时间点P < 0.05）， ASC组更有可能在12个月时达到疼痛VAS（50%对24%，P = 0.01）和PASS(45%对24%，P = 0.04)，在KOOS5中（43%对16%，P = 0.02），尽管在24个月时没有。与KL 4级OA患者相比，ASC治疗KL 2/3级OA患者的KOOS5评分（P = 0.01）和疼痛VAS评分（P = 0.03）明显优于KL 4级OA患者，但SVF治疗的膝关节无明显差异。3名接受ASCs的患者（7%，所有KL 3级）寻求额外的非手术治疗24个月，而9名接受SVF的患者（24%，所有KL 3级）（P = 0.06）。ASC强化注射没有额外的益处。值得注意的是，ASC队列患者在加强注射后报告的注射部位疼痛和肿胀比初始注射后更多（P < 0.01）。结论：这代表了ASCs和SVF治疗人类膝关节OA的首次正面比较。ASC和SVF注射在所有随访时间点都显著改善了膝关节疼痛和功能，尽管ASC注射在12个月时对疼痛VAS的MCID和PASS以及KOOS5的MCID有明显更好的改善。在初始治疗后，ASC强化注射似乎没有任何益处。考虑到较低的供体部位发病率和2年同等的优越结果，在治疗膝关节OA时使用ASCs优于SVF可能是合理的。
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.