Intra-articular Injection of Autologous Adipose-Derived Stem Cells or Stromal Vascular Fractions: Are They Effective for Patients With Knee Osteoarthritis? A Systematic Review With Meta-analysis of Randomized Controlled Trials

Am J Sports Med. 2023 Mar;51(3):837-848. doi: 10.1177/03635465211053893. Epub 2022 Jan 12.

Abstract

Background: Intra-articular injection of adipose-derived stem cells, which are divided into adipose-derived mesenchymal stem cells (ASCs) and adipose-derived stromal vascular fractions (ADSVFs), has been reported to be a viable treatment modality for knee osteoarthritis (OA); however, its efficacy remains limited.

Purpose: This study aimed to provide comprehensive information about the efficacy and safety of intra-articular injections of autologous ASCs and ADSVFs without adjuvant treatment in patients with knee OA.

Study design: Meta-analysis; Level of evidence, 1.

Methods: A systematic search of the MEDLINE, Embase, Web of Science, and Cochrane Library databases was performed to identify randomized controlled trials (RCTs) that evaluated the efficacy and safety of intra-articular injections of autologous ASCs or ADSVFs without adjuvant treatments compared with placebo or hyaluronic acid in patients with knee OA. Clinically, the 100-mm visual analog scale for pain relief and the Western Ontario and McMaster Universities Osteoarthritis Index for functional improvement were implemented. Radiologically, cartilage status was assessed using magnetic resonance imaging (MRI). Procedure-related knee pain, swelling, and adverse events (AEs) were evaluated for safety. Additionally, we performed subgroup analyses comparing ASCs versus ADSVFs. Methodological quality was assessed using the modified Coleman Methodology Score (mCMS).

Results: A total of 5 RCTs were included in this study. Based on the meta-analysis, ASCs or ADSVFs showed significantly better pain relief at 6 months (Z = 7.62; P < .0001) and 12 months (Z = 7.21; P < .0001) and functional improvement at 6 months (Z = 4.13; P < .0001) and 12 months (Z = 3.79; P = .0002), without a difference in procedure-related knee pain or swelling compared with controls. Although a meta-analysis with regard to cartilage improvements was not performed owing to heterogeneous MRI assessment, 3 studies reported significantly improved cartilage status after the injection. No serious AEs associated with ASCs or ADSVFs were reported. Subgroup analyses showed similar efficacy between ASC and ADSVF treatments. The median mCMS was 70 (range, 55-75).

Conclusion: For patients with knee OA, intra-articular injection of autologous ASCs or ADSVFs without adjuvant treatment showed remarkable clinical efficacy and safety at short-term follow-up. Some degree of efficacy has been shown for cartilage regeneration in knee OA, although the evidence remains limited. Further RCTs that directly compare ASCs and ADSVFs are needed.

Keywords: adipose tissue; adipose-derived stem cells; knee osteoarthritis; mesenchymal stem cell; stromal vascular fraction.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Injections, Intra-Articular
  • Mesenchymal Stem Cell Transplantation* / methods
  • Mesenchymal Stem Cells*
  • Osteoarthritis, Knee* / etiology
  • Pain / etiology
  • Randomized Controlled Trials as Topic
  • Treatment Outcome