Intra-Articular Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Phase IIb, Randomized, Placebo-Controlled Clinical Trial

Woo-Suk Lee, Hwan Jin Kim, Kang-Il Kim, Gi Beom Kim, Wook Jin, Woo-Suk Lee, Hwan Jin Kim, Kang-Il Kim, Gi Beom Kim, Wook Jin

Abstract

Mesenchymal stem cells (MSCs) have been the focus of an emerging treatment for osteoarthritis. However, few studies reported about outcomes of an intra-articular injection of autologous adipose-derived mesenchymal stem cells (AD-MSCs). This study aimed to assess the efficacy and safety of a single intra-articular injection of AD-MSCs for patients with knee osteoarthritis. It was a prospective double-blinded, randomized controlled, phase IIb clinical trial. AD-MSCs were administered for 12 patients (MSC group), and the group was compared with 12 knees with injection of normal saline (control group) up to 6 months. All procedures were performed in the outpatient clinic. Primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) score. Secondary outcome measure included various clinical and radiologic examination, and safety after injection. Change of cartilage defect after injection was evaluated using magnetic resonance imaging (MRI). Single injection of AD-MSCs led to a significant improvement of the WOMAC score at 6 months. In the control group, there was no significant change in the WOMAC score at 6 months. No serious adverse events were observed in both groups during the follow-up period. In MRI, there was no significant change of cartilage defect at 6 months in MSC group whereas the defect in the control group was increased. An intra-articular injection of autologous AD-MSCs provided satisfactory functional improvement and pain relief for patients with knee osteoarthritis in the outpatient setting, without causing adverse events at 6 months' follow-up. Larger sample size and long-term follow-up are required. Stem Cells Translational Medicine 2019;8:504-511.

Keywords: Adipose-derived mesenchymal stem cell; Intra-articular injection; Knee; Osteoarthritis.

Conflict of interest statement

W.S.L., W.J., and K.I.K. reported receiving research grants from R‐Bio Co., Ltd. The other authors indicated no potential conflicts of interest.

© 2019 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
Changes in the WOMAC score during the 6‐month period after intra‐articular injection in the MSC group and control group. Patients with injection of AD‐MSC showed significant improvement in the WOMAC score. Patients in the control group did not significantly change in the WOMAC score. (A): The WOMAC total score. (B): The pain subscore of the WOMAC. (C): The stiffness subscore of the WOMAC. (D): The physical function subscore of the WOMAC. Abbreviations: MSC, mesenchymal stem cell; WOMAC, Western Ontario and McMaster Universities Osteoarthritis index.
Figure 3
Figure 3
Changes in VAS for knee pain and KOOS score during the 6‐month period after intra‐articular injection in the MSC group and control group. The VAS and all subscores of the KOOS significantly increased over 6 months compared with baseline in only the MSC group. There were no significant improvements in the VAS and all subscores of the KOOS in the control group. (A): VAS for knee pain. (B): The pain subscore of the KOOS. (C): The symptoms subscore of the KOOS. (D): The activities of daily living subscore of the KOOS. (E): The sports subscore of the KOOS. (F): The quality of life subscore of the KOOS. Abbreviations: KOOS, Knee Injury and Osteoarthritis Outcome Score; MSC, mesenchymal stem cell; VAS, visual analog scale.
Figure 4
Figure 4
MRI evaluation of the size of cartilage defect in the MSC group and control group at baseline and at 3 and 6 months after injection. (A): Coronal and sagittal images of the medial femoral and tibial condyles before, 3 months after, and 6 months after injection of AD‐MSCs. The size of cartilage defect of the medial femoral condyle in serial MRI scans did not change over 6 months of follow‐up. (B): Coronal and sagittal images of the femoral and tibial condyles before, 3 months after, and 6 months after injection of normal saline. The size of cartilage defect of the medial femoral condyle in serial MRI scans significantly increased over 6 months of follow‐up. Abbreviations: AD‐MSCs, adipose‐derived mesenchymal stem cells; MRI, magnetic resonance imaging; MSC, mesenchymal stem cell.

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