Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II)

Lamo-Espinosa JM, Mora G, Blanco JF, et al. · Journal of Translational Medicine

VAS carries the trial's only between-group tests, and both cell arms cleared control at 12 months (low dose p=0.005, high dose p<0.009), medians falling from 7 and 6 to 2 and 2 against 5 to 4 on control. The WOMAC results are within-group: the figure and table asterisks are marked as against each group's own baseline, and the widely quoted 16.5-point high-dose gain (IQR 12 to 19, p<0.01) is one such. The same results section, subtracting each patient's 12-month score from their baseline, gives the high-dose median as -14 (-15, -8) against -14 (-27, 4) on the low dose and -6.5 (-19, 4) on control - so the paper states its headline WOMAC figure two ways. Joint space narrowed on control at borderline significance (p=0.05) and did not on the high dose; the low-dose arm could not be assessed because its baseline value was 0. WORMS MRI improved by a median 4 points on the high dose only. The two cell doses were never compared with each other.

Population

30 patients with KL grade 2-4 knee OA, multicenter

Intervention

Culture-expanded autologous BM-MSCs (10 or 100 million cells) plus HA

Comparator

Hyaluronic acid alone

Limitations

Phase I/II with 10 patients per arm; unblinded; HA co-administered with the cells confounds attribution. Funded by the Instituto de Salud Carlos III and regional public bodies, with no competing interests declared. At 4 years the same cohort showed no clinical difference between the two doses, and WOMAC separated from control in the low-dose arm rather than the high one.