Stromal cell-based injection therapies for the treatment of knee osteoarthritis: A systematic review of level I randomized controlled trials

Jaydeep Dhillon; James A Maguire; Matthew J Kraeutler

doi:10.1016/j.ocarto.2025.100608

Stromal cell-based injection therapies for the treatment of knee osteoarthritis: A systematic review of level I randomized controlled trials

Osteoarthr Cartil Open. 2025 Apr 9;7(2):100608. doi: 10.1016/j.ocarto.2025.100608. eCollection 2025 Jun.

Authors

Jaydeep Dhillon¹, James A Maguire², Matthew J Kraeutler³

Affiliations

¹ Samaritan Health Services, Department of Orthopedics, Corvallis, OR 97330, USA.
² St. Joseph's University Medical Center, Department of Orthopaedic Surgery, Paterson, NJ 07503, USA.
³ Texas Tech University Health Sciences Center, Department of Orthopaedic Surgery & Rehabilitation, Lubbock, TX 79430, USA.

Abstract

Objective: To systematically review randomized controlled trials (RCTs) to compare clinical outcomes of stromal cell-based injection therapies versus other non-operative treatment modalities for the treatment of knee osteoarthritis (OA).

Method: A systematic review was performed by searching PubMed, Cochrane Library, and EMBASE to locate RCTs, published since 2019, comparing stromal cell-based injection therapies versus other non-operative modalities for the treatment of knee OA. The search terms used were: knee AND osteoarthritis AND injection AND randomized.

Results: Seventeen studies (all Level I evidence) were included in this review with 972 patients undergoing treatment with stromal cell-based therapy (Intervention Group) and 651 patients in the control group (Control Group). Among the 17 studies, 7 used autologous adipose-derived mesenchymal stromal cells (MSCs) (ADMSCs), 2 studies used allogeneic ADMSCs, 4 used autologous bone marrow-derived MSCs (BMMSCs), 1 used allogeneic BMMSCs, 1 used allogeneic placental MSCs, 1 used umbilical cord-derived MSCs (UCMSCs), and 1 study used autologous ADMSCs, BMMSCs, or allogeneic UCMSCs. All but 3 studies reported significantly better clinical or radiological outcomes in the Intervention Group at final follow-up. A total of 5 and 3 studies reported adverse events occurring in the Intervention and the Control groups, respectively, but they were all self-limiting.

Conclusions: Patients undergoing treatment of knee OA with MSCs might be expected to experience improvements in clinical and radiological outcomes in comparison to other non-operative modalities. Additional studies with mid-to long-term outcomes are needed to better determine the efficacy and safety of MSCs for the treatment of knee OA.

Keywords: Injection therapy; Knee osteoarthritis; Stromal stem cells.