Table 2.
Randomized clinical trials (RCTs) on the effectiveness of intraarticular injections of MSCs in knee OA.
| Authors [Reference] | Year | Methods and Results | Participants | Level of Evidence |
Conclusions |
|---|---|---|---|---|---|
| Vega et al. [56] | 2015 | These authors randomized 30 subjects with chronic knee pain unresponsive to conservative management and exhibiting radiological evidence of OA into two cohorts of 15 subjects. The test cohort was treated with allogeneic bone marrow MSCs by intra-articular injection of 40 × 10(6) cells. The control cohort received intra-articular hyaluronic acid (60 mg, single dose). | 30 patients | NA | Allogeneic MSC treatment might be a valid option for the treatment of chronic knee OA. The procedure was simple, did not need surgery, provided pain alleviation, and substantially ameliorated cartilage quality. |
| Lamo-Espinosa et al. [57] | 2018 | In this phase I/II multicenter randomized clinical trial with active control, no complications were found after autologous bone marrow-derived MSCs (BM-MSCs) administration or during the follow-up. BM-MSCs-administered subjects improved according to VAS at the end of follow up. | 30 patients | NA | Single intraarticular injection of in vitro expanded autologous BM-MSCs was a safe and feasible technique that resulted in long-run clinical and functional amelioration of knee OA. |
| Matas et al. [58] | 2019 | Subjects with symptomatic knee OA were randomized to receive hyaluronic acid at baseline and 6 months (hyaluronic acid, n = 8), single-dose (20 × 106) UC-MSC at baseline (MSC-1, n = 9), or repeated UC-MSC doses at baseline and 6 months (20 × 106 × 2; MSC-2, n = 9). | 26 patients | NA | In this phase I/II trial, repeated UC-MSC therapy was safe and better than the comparative group at 1-year follow-up. |
| Lee et al. [59] | 2019 | Single injection of AD-MSCs led to a substantial amelioration of the WOMAC score at 6 months. In the control group, there was no significant change in the WOMAC score at 6 months. | 24 patients | NA | An intraarticular injection of autologous AD-MSCs rendered satisfactory functional amelioration and pain alleviation for subjects with knee OA without causing complications at 6-month follow-up. |
| Lamo-Espinosa et al. [60] | 2020 | These authors assessed the clinical impact of a dose of 100 × 106 cultured autologous BM-MSCs in combination with PRP (PRGF®) as adjuvant. No complications were found after BM-MSC administration or during follow-up. | 60 patients | NA | Treatment with BM-MSC associated with PRGF® was shown to be a viable therapeutic option for OA of the knee, with clinical improvement at the end of follow-up. |
| Bastos et al. [61] | 2020 | This study compared the clinical and laboratory results of intraarticular injections of culture-expanded bone-derived MSCs with or without PRP to intraarticular corticosteroid injections for the management of knee OA. | 47 patients | II | An intraarticular injection of bone marrow-derived culture-expanded MSCs with or without the addition of PRP was efficacious in ameliorating the diminishing function and symptoms caused by knee OA at 12-month follow-up. |
| Hernigou et al. [62] | 2021 | These authors compared subchondral bone to intraarticular injection of bone marrow concentrate MSCs in bilateral knee OA. The aim was to determine which one of them was better at postponing TKA at 15 years. | 60 patients (120 knees) | NA | Implantation of MSCs in the subchondral bone of an osteoarthritic knee was more efficacious at delaying TKA than injection of the same intraarticular dose in the contralateral knee with the same degree of OA. |
MSCs = Mesenchymal stem cells; OA = Osteoarthritis; n = Number of patients; LoE = Level of evidence; BM-MSCs = Bone marrow-derived MSCs; UC-MSCs = umbilical cord-derived MSCs; AD-MSCs = Adipose tissue-derived MSCs; PRP = Platelet-rich plasma; TKA = total knee arthroplasty; NA = Not available.