Adipose- and bone marrow-derived stromal cells reduce pain in patients with knee osteoarthritis but do not substantially improve knee functionality : an updated systematic review and meta-analysis
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Springer
Abstract
PURPOSE : To perform a systematic review and meta-analysis of randomized and comparative studies comparing mesenchymal stromal cells other orthobiological injections for patients with knee osteoarthritis.
METHODS : Systematic review of Medline, Embase, Scopus, and Google Scholar, including all level 1–3 from 2014 to 2024. Validated scores (VAS, KOOS, Lysholm, IKDC) were included as outcome measures. Risk of bias was assessed using the Cochrane Collaboration’s tools. The GRADE system was used to assess the quality of the body of evidence and the modified Coleman Methodology score was used to assess study quality. Heterogeneity was assessed using χ2 and I2 statistics.
RESULTS : Ten studies were included; all published in English between 2019 and 2023, encompassing a total of 563 cases (281 treated with MSCs and 282 with other biologics). Two studies had a high risk of bias, one had some bias, and seven had a low risk of bias. Publication bias was detected (Egger's test 3.26447; p = 0.007). The pooled estimates revealed significant differences favoring MSCs for VAS scores at 3, 6, and 12 months. For KOOS pain and symptoms, significant differences were observed at 3 and 6 months.
CONCLUSION : The results of this meta-analysis demonstrated a significant effect of adipose and bone marrow-derived stromal cell injections on pain reduction at all assessed time points, and showed superiority over other non-surgical treatment options. These differences were not reflected in clinical and functional outcomes, indicating that the observed reduction in pain did not correspond to substantial improvements in knee functionality.
Description
DATA AVAILABILITY : No datasets were generated or analysed during the current study.
SUPPLEMENTARY FIGURE 1: PRISMA Flow Diagram. From the initial 1576 records, 10 studies were included in the quantitative synthesis. SUPPLEMENTARY FIGURE 2: The funnel plot exhibited asymmetry in the standard deviations of the means, suggesting the presence of publication bias. SUPPLEMENTARY FIGURE 3: The Forest Plot did not demonstrate significant between group differences at baseline. SUPPLEMENTARY FIGURE 4: Forest Plot comparing VAS at 12 months demonstrated between group significant differences (p=0.001) in favor of MSCs. SUPPLEMENTARY FIGURE 5: Forest Plot comparing the KOOS subscale pain at baseline demonstrated significant between group differences in favor of the control group (p=0.02). SUPPLEMENTARY FIGURE 6: Forest Plot comparing the KOOS subscale symptoms at baseline did not demonstrate significant between group differences. SUPPLEMENTARY FIGURE 7: Forest Plot comparing the KOOS subscale ADL at baseline could not demonstrate significant between group differences (p=0.511). SUPPLEMENTARY FIGURE 8: Forest Plot comparing the KOOS subscale sports at baseline could not demonstrate significant between group differences (p=0.298). SUPPLEMENTARY FIGURE 9: Forest Plot comparing the KOOS subscale QOL at baseline could not demonstrate significant between group differences (p=0.272) SUPPLEMENTARY FIGURE 10: Forest Plot comparing the total WOMAC score at baseline could not demonstrate significant between group differences (p=0.215). SUPPLEMENTARY FIGURE 11: Forest Plot comparing the WOMAC subscore pain at baseline did not demonstrate significant between group differences (p=0.169). SUPPLEMENTARY FIGURE 12: Forest Plot comparing the WOMAC subscore pain at 3 months did not demonstrate significant between group differences (p=0.448). SUPPLEMENTARY FIGURE 13: Forest Plot comparing the WOMAC sub-score pain at 6 months did not demonstrate significant between group differences (p=0.162). SUPPLEMENTARY FIGURE 14: Forest Plot comparing the WOMAC subscore pain at 12 months did not demonstrate significant between group differences (p=0.204). SUPPLEMENTARY FIGURE 15: Forest Plot comparing the WOMAC subscore stiffness at baseline did not demonstrate significant between group differences (p=0.119). SUPPLEMENTARY FIGURE 16: Forest Plot comparing the WOMAC subscore stiffness at 3 months demonstrated near significant between group differences in favor of MSCs (p=0.072). SUPPLEMENTARY FIGURE 17: Forest Plot comparing the WOMAC subscore stiffness at 6 months did not demonstrate significant between group differences (p=0.678). SUPPLEMENTARY FIGURE 18: Forest Plot comparing the WOMAC subscore stiffness at 12 months did not demonstrate significant between group differences (p=0.856). SUPPLEMENTARY FIGURE 19: Forest Plot comparing the WOMAC subscore function at baseline did not demonstrate significant between group differences (p=0.082). SUPPLEMENTARY FIGURE 20: Forest Plot comparing the WOMAC subscore function at 3 months did not demonstrate significant between group differences (p=0.946). SUPPLEMENTARY FIGURE 21: Forest Plot comparing the WOMAC subscore function at 6 months did not demonstrate significant between group differences (p=0.112). SUPPLEMENTARY FIGURE 22: Forest Plot comparing the WOMAC subscore function at 12 months did not demonstrate significant between group differences (p=0.488).
SUPPLEMENTARY FIGURE 1: PRISMA Flow Diagram. From the initial 1576 records, 10 studies were included in the quantitative synthesis. SUPPLEMENTARY FIGURE 2: The funnel plot exhibited asymmetry in the standard deviations of the means, suggesting the presence of publication bias. SUPPLEMENTARY FIGURE 3: The Forest Plot did not demonstrate significant between group differences at baseline. SUPPLEMENTARY FIGURE 4: Forest Plot comparing VAS at 12 months demonstrated between group significant differences (p=0.001) in favor of MSCs. SUPPLEMENTARY FIGURE 5: Forest Plot comparing the KOOS subscale pain at baseline demonstrated significant between group differences in favor of the control group (p=0.02). SUPPLEMENTARY FIGURE 6: Forest Plot comparing the KOOS subscale symptoms at baseline did not demonstrate significant between group differences. SUPPLEMENTARY FIGURE 7: Forest Plot comparing the KOOS subscale ADL at baseline could not demonstrate significant between group differences (p=0.511). SUPPLEMENTARY FIGURE 8: Forest Plot comparing the KOOS subscale sports at baseline could not demonstrate significant between group differences (p=0.298). SUPPLEMENTARY FIGURE 9: Forest Plot comparing the KOOS subscale QOL at baseline could not demonstrate significant between group differences (p=0.272) SUPPLEMENTARY FIGURE 10: Forest Plot comparing the total WOMAC score at baseline could not demonstrate significant between group differences (p=0.215). SUPPLEMENTARY FIGURE 11: Forest Plot comparing the WOMAC subscore pain at baseline did not demonstrate significant between group differences (p=0.169). SUPPLEMENTARY FIGURE 12: Forest Plot comparing the WOMAC subscore pain at 3 months did not demonstrate significant between group differences (p=0.448). SUPPLEMENTARY FIGURE 13: Forest Plot comparing the WOMAC sub-score pain at 6 months did not demonstrate significant between group differences (p=0.162). SUPPLEMENTARY FIGURE 14: Forest Plot comparing the WOMAC subscore pain at 12 months did not demonstrate significant between group differences (p=0.204). SUPPLEMENTARY FIGURE 15: Forest Plot comparing the WOMAC subscore stiffness at baseline did not demonstrate significant between group differences (p=0.119). SUPPLEMENTARY FIGURE 16: Forest Plot comparing the WOMAC subscore stiffness at 3 months demonstrated near significant between group differences in favor of MSCs (p=0.072). SUPPLEMENTARY FIGURE 17: Forest Plot comparing the WOMAC subscore stiffness at 6 months did not demonstrate significant between group differences (p=0.678). SUPPLEMENTARY FIGURE 18: Forest Plot comparing the WOMAC subscore stiffness at 12 months did not demonstrate significant between group differences (p=0.856). SUPPLEMENTARY FIGURE 19: Forest Plot comparing the WOMAC subscore function at baseline did not demonstrate significant between group differences (p=0.082). SUPPLEMENTARY FIGURE 20: Forest Plot comparing the WOMAC subscore function at 3 months did not demonstrate significant between group differences (p=0.946). SUPPLEMENTARY FIGURE 21: Forest Plot comparing the WOMAC subscore function at 6 months did not demonstrate significant between group differences (p=0.112). SUPPLEMENTARY FIGURE 22: Forest Plot comparing the WOMAC subscore function at 12 months did not demonstrate significant between group differences (p=0.488).
Keywords
Mesenchymal stromal cells, Orthobiological injections, Patients, Knee osteoarthritis, Orthobiologics, Adipose derived stem cells, Bone marrow derived stem cells, Bone marrow derived stromal cells, Adipose derived stromal cells
Sustainable Development Goals
SDG-03: Good health and well-being
Citation
Hohmann, E., Keough, N., Stokes, D. et al. Adipose- and bone marrow-derived stromal cells reduce pain in patients with knee osteoarthritis but do not substantially improve knee functionality: an updated systematic review and meta-analysis. European Journal of Orthopaedic Surgery and Traumatology 35, 214 (2025). https://doi.org/10.1007/s00590-025-04322-4.