Intra-articular Injection of Mesenchymal Stem Cells for the Treatment of Osteoarthritis of the Knee: A Proof-of-Concept Clinical Trial
Translational and Clinical Research
Translational and Clinical Research Doi: 10.1002/stem.1634
Chris Hyunchul Jo1, Young Gil Lee1, Won Hyoung Shin1, Hyang Kim1, Jee Won Chai2, Eui Cheol Jeong3, Ji Eun Kim4, Hackjoon Shim5, Ji Sun Shin1, Il Seob Shin6, Jeong Chan Ra6, Sohee Oh7, and Kang Sup Yoon1*
1Department of Orthopedic Surgery, 2Department of Radiology, 3Department of Plastic and Reconstructive Surgery,4Department of Pathology, Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 156-707, Korea; 5Cardiovascular Research Institute, Yonsei University College of Medicine, 250 Seongsanno, Seodaemung-gu, Seoul, 120-752, Korea; 6Stem Cell Research Center, K-STEM CELL, 1596-7 Nakseongdae-dong, Gwanak-gu, Seoul, 151-835, Korea; 7Department of Biostatistics, SMG-SNU Boramae Medical Center, Seoul, Korea.
Mesenchymal stem cells are known to have a potential for articular cartilage regeneration. However, most studies focused on focal cartilage defect through surgical implantation. For the treatment of generalized cartilage loss in osteoarthritis, an alternative delivery strategy would be more appropriate. The purpose of this study was to assess the safety and efficacy of intra-articular injection of autologous adipose tissue derived MSCs (AD-MSCs) for knee osteoarthritis. We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee. The phase I study consists of 3 dose-escalation cohorts; the low-dose (1.0×107 cells), mid-dose (5.0×107) and high-dose (1.0×108) group with 3 patients each. The phase II included 9 patients receiving the high-dose. The primary outcomes were the safety and the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) at 6 months. Secondary outcomes included clinical, radiological, arthroscopic, and histological evaluations. There was no treatment-related adverse event. The WOMAC score improved at 6 months after injection in the high-dose group. The size of cartilage defect decreased while the volume of cartilage increased in the medial femoral and tibial condyles of the high-dose group. Arthroscopy showed that the size of cartilage defect decreased in the medial femoral and medial tibial condyles of the high-dose group. Histology demonstrated thick, hyaline-like cartilage regeneration. These results showed that intra-articular injection of 1.0×108 AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events, and reduced cartilage defects by regeneration of hyaline-like articular cartilage.
In summary, intra-articular injection of 1.0x108AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events. Radiological, arthroscopic, and histological measures consistently demonstrated decreased of articular cartilage defects by regeneration of hyaline-like articular cartilage. These results are promising to encourage large randomized clinical trials, and we are cautiously optimistic about this new step for the treatment of osteoarthritis of the knee.