Published online Apr 18, 2026. doi: 10.5312/wjo.v17.i4.116916
Revised: December 23, 2025
Accepted: February 9, 2026
Published online: April 18, 2026
Processing time: 137 Days and 3 Hours
Knee osteoarthritis (KOA) is a major cause of disability, especially among older adults and individuals with obesity. Mesenchymal stromal cells (MSCs), particularly those derived from peripheral blood (PB)-MSCs, offer a minimally invasive alternative to bone marrow-derived MSCs for cartilage repair, with comparable chondrogenic potential and reduced procedural risks. However, optimal delivery routes remain underexplored.
To compare clinical and radiological outcomes of intra-articular, subchondral, and combined PB-MSC injections in patients with primary KOA through a double-blinded, unicentric randomized controlled trial.
A total of 150 patients with Kellgren-Lawrence grade 2 or 3 KOA will be randomized into three groups: Intra-articular (group A), subchondral (group B), and combined (group C) PB-MSC injections. PB-MSCs will be harvested post-Filgrastim stimulation via density centrifugation. Functional scores (Visual Analog Scale, Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, International Knee Documentation Committee) and imaging (magnetic resonance cartigram, Magnetic Resonance Observation of Cartilage Repair Tissue) will be assessed over 12 months.
Interim results will show that all three PB-MSC delivery routes will improve pain and function in primary KOA. Combined intra-articular plus subchondral injections will demonstrate superior gains in Visual Analog Scale, Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, and International Knee Documentation Committee scores, with magnetic resonance imaging expected to confirm better cartilage integrity. Adverse events will be reported, supporting the anticipated safety and regenerative efficacy of PB-MSC therapy.
Identifying the most effective PB-MSC delivery route is central to optimizing regenerative strategies for early-grade knee osteoarthritis. By comparing intra-articular, subchondral, and combined injection techniques, the trial seeks to enhance patient mobility, alleviate pain, and delay disease progression - ultimately informing evidence-based protocols tailored to the Indian clinical landscape.
Core Tip: Optimizing delivery routes for peripheral blood-derived mesenchymal stromal cells is key to enhancing regenerative outcomes in early-grade knee osteoarthritis. This trial compares intra-articular, subchondral, and combined injection techniques using clinical scores and advanced imaging over 12 months. The goal is to establish minimally invasive, evidence-based protocols that improve function, reduce pain, and delay progression - aligned with the Indian healthcare context and regenerative medicine advancements.