Treatment of knee osteoarthritis with intra-articular injection of autologous adipose-derived mesenchymal progenitor cells: a prospective, randomized, double-blind, active-controlled, phase IIb clinical trial

Liangjing Lu, Chengxiang Dai, Zhongwen Zhang, Hui Du, Suke Li, Ping Ye, Qiong Fu, Li Zhang, Xiaojing Wu, Yuru Dong, Yang Song, Dongbao Zhao, Yafei Pang, Chunde Bao, Liangjing Lu, Chengxiang Dai, Zhongwen Zhang, Hui Du, Suke Li, Ping Ye, Qiong Fu, Li Zhang, Xiaojing Wu, Yuru Dong, Yang Song, Dongbao Zhao, Yafei Pang, Chunde Bao

Abstract

Objective: Human adipose-derived mesenchymal progenitor cells (haMPCs) are stem cells with multiple differentiation potential and immunomodulatory function. Re-Join® comprises in vitro expanded haMPCs from adipose tissue of patients combined with cell suspension solution. This study was undertaken to evaluate the efficacy and safety of Re-Join® in patients with symptomatic knee osteoarthritis (OA).

Methods: Patients with Kellgren-Lawrence grade 1-3 knee OA were recruited from two centers and randomized to receive intra-articular injection of Re-Join® or HA. Pain and function were assessed by using WOMAC score, VAS, and SF-36. Magnetic resonance imaging (MRI) analysis was performed to measure cartilage repair. Adverse events (AEs) were collected.

Results: Fifty-three patients were randomized. Significant improvements in WOMAC, VAS, and SF-36 scores were observed in both groups at months 6 and 12 compared with baseline. Compared with the HA group, significantly more patients achieved 50% improvement of WOMAC and a trend of more patients achieved a 70% improvement rate in Re-Join® group after 12 months. Meanwhile, there was notably more increase in articular cartilage volume of both knees in the Re-Join® group than in the HA group after 12 months as measured by MRI. AEs were comparable between two groups. Most AEs were mild and moderate except one SAE of right knee joint infection in the HA group.

Conclusions: Significant improvements in joint function, pain, quality of life, and cartilage regeneration were observed in Re-Join®-treated knee OA patients with good tolerance in a period of 12 months.

Trial registration: ClinicalTrials.gov Identifier: NCT02162693 . Registered 13 June 2014.

Keywords: Intra-articular injection; Knee osteoarthritis; Magnetic resonance imaging; Mesenchymal stem cells; WOMAC.

Conflict of interest statement

Chengxiang Dai, Suke Li, and Li Zhang are current employees and stock option holders of the Cellular Biomedicine Group (Nasdaq: CBMG). The other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of the clinical trial
Fig. 2
Fig. 2
Changes of WOMAC score during 12 months after intra-articular injection of Re-Join® and HA. a Score and mean improvement rate of WOMAC, VAS, and SF-36 in the Re-Join® and HA groups at baseline and 6 months and 12 months after injection. b Mean improvement rate of WOMAC score compared with baseline in the Re-Join® and HA groups at baseline and 6 months and 12 months after injection. Statistics were determined by t test in a and b. c, d Number of patients who reached an improvement rate of 20%, 50%, and 70% according to the WOMAC score in 6 months (c) and 12 months (d) after injection compared with baseline. Score was shown in mean and standard deviation. Mean improvement rate was shown as the percentage of change of score in each time point of follow-up compared with baseline. Statistics were determined by χ2 test in c and d. *P < 0.05, **P < 0.01, ***P < 0.001
Fig. 3
Fig. 3
Changes of VAS and SF-36 scores during 12 months after intra-articular injection of Re-Join® and HA. a VAS score for the left knee in the Re-Join® and HA groups at baseline and 6 months and 12 months after injection. b VAS score for the right knee in the Re-Join® and HA groups at baseline and 6 months and 12 months after injection (c). SF-36 score in the Re-Join® and HA groups at baseline and 6 months and 12 months after injection. Data was shown in mean and standard deviation. Statistics were determined by t test. *P < 0.05, **P < 0.01, ***P < 0.001
Fig. 4
Fig. 4
Changes of articular cartilage volume by MRI during 12 months after intra-articular injection of Re-Join® and HA. a, b Representative MRI images of the knee joint before and after treatment with Re-Join®. Sagittal views at the height of the patella-femoral condyles before and after 12 months of treatment. The arrows indicate the zones in which treatment generated a mild change in terms of cartilage thickness. c Changes of left knee cartilage volume by MRI in the Re-Join@ and HA groups at baseline and 6 months and 12 months after injection. d Change of right knee cartilage volume by MRI in the Re-Join@ and HA groups at baseline and 6 months and 12 months after injection. e Changes of left knee cartilage volume by MRI of different anatomy location in 6 months after injection. f Changes of right knee cartilage volume by MRI of different anatomy location in 6 months after injection. g Changes of left knee cartilage volume by MRI of different anatomy location in 12 months after injection. h Changes of right knee cartilage volume by MRI of different anatomy location in 12 months after injection. Data was shown in mean and standard deviation. Statistics were determined by Wilcoxon signed rank test. Baseline was shown as 0d, changes of knee cartilage volume were shown as Δ6mw-0d and Δ12m-0d. *P < 0.05, **P < 0.01, ***P < 0.001

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