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. 2022 Jun 22;11(6):586-596.
doi: 10.1093/stcltm/szac024.

Safety and Efficacy of the Intra-articular Injection of Mesenchymal Stem Cells for the Treatment of Osteoarthritic Knee: A 5-Year Follow-up Study

Kang-Il Kim  1   2 , Woo-Suk Lee  3 , Jun-Ho Kim  1 , Jung-Kwon Bae  1 , Wook Jin  4
Affiliations

Safety and Efficacy of the Intra-articular Injection of Mesenchymal Stem Cells for the Treatment of Osteoarthritic Knee: A 5-Year Follow-up Study

Kang-Il Kim et al. Stem Cells Transl Med. .

Abstract

Although successful short-term results of the intra-articular injection of mesenchymal stem cells (MSCs) for the conservative treatment of knee osteoarthritis (OA) have been reported, the mid-term results of the injection of adipose-derived (AD) MSCs remains unknown. We assessed the mid-term safety and efficacy of the intra-articular injection of ADMSCs in patients with knee OA. Eleven patients with knee OA were prospectively enrolled and underwent serial evaluations during a 5-year follow-up of a single intra-articular injection of autologous high-dose (1.0 × 108) ADMSCs. The safety profiles were assessed using the World Health Organization Common Toxicity Criteria. The clinical evaluations included visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain and function, respectively. The radiologic evaluations included chondral defect area and whole-organ magnetic resonance imaging scores (WORMS) by serial magnetic resonance imaging (MRI). Hip-knee-ankle axis (HKAA) and Kellgren-Lawrence (K-L) grades were assessed on simple radiographs. No treatment-related adverse events occurred during the 5-year follow-up. Both VAS and total WOMAC scores improved significantly at 6 months after the injection and until the latest follow-up. Total WORMS was significantly improved until 3 years after the injection. However, the chondral defect size on MRI or other radiologic evaluations did not change significantly. A single intra-articular injection of autologous, high-dose ADMSCs provided safe and clinical improvement without radiologic aggravation for 5 years. Furthermore, structural changes in the osteoarthritic knee showed significant improvement up to 3 years, suggesting a possible option for disease-modifying outpatient treatment for patients with knee OA.

Keywords: WORMS; a mid-term follow-up; adipose-derived mesenchymal stem cell; disease-modifying treatment; intra-articular injection; knee osteoarthritis.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Study flow diagram of prior phase IIb clinical trial and retrospective analysis of prospectively collected data from the prior clinical trial. Abbreviation: ADMSC, adipose tissue-derived mesenchymal stem cell.
Figure 2.
Figure 2.
Changes in the VAS for pain and the WOMAC scores for function at 6, 12, 24, 36, 48, and 60 months after intra-articular injection of ADMSCs from baseline (pre-injection) showing that VAS for pain (A), total WOMAC scores (B), pain sub-score of WOMAC (C), and function sub-score of WOMAC (E) had shown significant improvements until 5 years after the injection of ADMSCs. Stiffness sub-sub-score of WOMAC (D) had shown significant improvement until 3 years after the injection of ADMSCs. *Indicates statistically significant difference from baseline (P < .05). Abbreviations: ADMSC, adipose-derived mesenchymal stem cell; F/U, follow-up; VAS, visual analog scale; Western Ontario and McMaster Universities Osteoarthritis Index.
Figure 3.
Figure 3.
Changes in hip-knee-ankle angle (A) and proportion of Kellgren-Lawrence grade (B), demonstrating no significant change after intra-articular injection of ADMSCs during 5 years of follow-up. Abbreviation: ADMSC, adipose-derived mesenchymal stem cell.
Figure 4.
Figure 4.
Changes in the simple radiographs and articular cartilage defects in MRI after intra-articular injection of ADMSCs are shown. The right knee of a 52-year-old female shows osteoarthritic knee of Kellgren-Lawrence grade 3 on standing anteroposterior and lateral radiographs, and 4° varus alignment of hip-knee ankle angle on teleradiograph of the lower extremity at baseline (A). Changes in cartilage defect on coronal and sagittal images MRI scans of the medial femoral and tibial condyles before and 2, 3, 4, and 5 years after the injection of AMDSCs are shown (B). The cartilage defect area has been restored and the irregular surface of the articular cartilage has been changed into a congruent surface at 2, 3, 4, and 5 years after the injection of ADMSCs. At 5-year follow-up, no change is observed in simple radiographs, showing still Kellgren-Lawrence grade 3 and 4° varus alignment (C). Abbreviations: ADMSC, adipose-derived mesenchymal stem cell; MRI, magnetic resonance image.
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