Long-term efficacy of autologous bone marrow mesenchymal stromal cells for treatment of knee osteoarthritis

Abstract

Knee osteoarthritis is the most prevalent joint disease and a frequent cause of pain, functional loss and disability. Conventional treatments have demonstrated only modest clinical benefits whereas cell-based therapies have shown encouraging results, but important details, such as dose needed, long-term evolution or number of applications required are scarcely known. Here we have reanalyzed results from two recent pilot trials with autologous bone marrow-derived mesenchymal stromal cells using the Huskisson plot to enhance quantification of efficacy and comparability. We find that cell doses of 10, 40 and 100 million autologous cells per knee provided quite similar healing results and that much of the effect attained 1 year after cell application remained after 2 and 4 years. These results are encouraging because they indicate that, apart from safety and simplicity: (i) the beneficial effect is both significant and sizeable, (ii) it can be achieved with a single injection of cells, and (iii) the effect is perdurable for years.Trial registration: EudraCT 2009-017405-11; NCT02123368. Registered 25 April 2014-Prospectively registered, https://ichgcp.net/clinical-trials-registry/NCT02123368?term=02123368&draw=2&rank=1.

Keywords: Intraarticular injection; Mesenchymal stem cells; Osteoarthritis; Regenerative medicine; Stem cell therapy.

Conflict of interest statement

J.G.S. is member of the Board of Directors of Citospin, a spin-off company of the University of Valladolid (Spain) that specializes in GMP-compliant cell production. M.A. and V.G. are employees of Citospin. The other authors declare that they have no conflicts of interest.

© 2021. The Author(s).

Figures

Fig. 1

Effects of BM-MSC treatment on pain (A, estimated from VAS) and disability (B, estimated from WOMAC, general index), both quantified as % of the maximum. Values (mean ± s.e.m. of 8–9 values) before cell treatment (t = 0; in red), 1 year after treatment (t = 1 yr, in green) and 4 years after treatment (t = 4 yr, in blue) are compared in the controls (Gr. 1, hyaluronic acid) and in the cell-treated groups (Gr. 2 and Gr. 3, treated with either 10 or 100 million cells suspended in hyaluronic acid, respectively). Statistical significance was assayed by repeated measurements one-way ANOVA, Bonferroni multiple comparisons; NS, not significant, *p < 0.05; **p < 0.01, ***p < 0.001

Fig. 2

Estimation of the efficacy of the different OA treatments from the Huskisson plot. Data were fitted to a straight line forced to pass through the origin. The slope measures the efficacy of the treatment, and values are given at the right side of the lines. Results from VAS (A, C, E) and WOMAC (B, D, F) in control patients not treated with cells (A, B), and patients treated with either 10 (C, D) or 100 million cells (E, F) are compared. Results 1 and 4 years after cell application are given (black circles and red inverted triangles, respectively). The blue dashed lines represent no effect (horizontal, slope 0) and perfect treatment (45 degrees, slope, 1). Linear regression analysis and statistical significance of the slope (difference from 0) is given. NS, not significant, *p < 0.05; **p < 0.01, ***p < 0.001; ****p < 0.0001