The Safety & Feasibility Study of Intra-Articular Transplantation of Wharton’s Jelly-Derived Mesenchymal Stromal Cells in Patients with Knee Osteoarthritis: Clinical Trial Phase I/IIa

The aim of this study is to evaluate the safety and feasibility of intra‑articular transplantation of Wharton’s jelly–derived mesenchymal stromal cells in patients with knee osteoarthritis, within a Phase I/IIa trial.

A two‑arm, randomized, controlled Phase I/II clinical trial conducted in 20 patients. Randomization will be performed using a computer‑generated random sequence.

This study will be conducted at Imam Khomeini Hospital, Karaj. Eligible participants who enter the study will be allocated to one of the two study groups according to the randomization table. The trial will follow a single‑blind design.

Inclusion Criteria Age 18–70 years. Both sexes. Knee osteoarthritis Kellgren–Lawrence grade II or III in early stages, confirmed by standing knee radiography. Knee joint malalignment less than 20°, determined by three‑joint view radiography. Patient Visual Analog Scale (VAS) ≥ 4. Inadequate response to standard treatment during the previous 3 months. Provision of written informed consent. Exclusion Criteria BMI higher than 35 kg/m². History of recent knee surgery or imminent need for joint replacement. Intra‑articular injection within the past 3 months. Coagulopathy or current use of anticoagulant medications. Requirement for systemic corticosteroid therapy. Immunodeficiency disorders. Severe allergy to protein/biologic products. Pregnancy or breastfeeding. Simultaneous participation in another clinical trial. Active systemic infection or infection of the knee joint. Substance abuse. Uncontrolled comorbid diseases.

Intervention Group: 20 million Wharton’s jelly–derived mesenchymal stromal cells (WJ‑MSCs) suspended in 3 mL of normal saline Control Group: A single dose of high‑molecular‑weight sodium hyaluronate

Safety; Feasibility

Allocation method Participants who meet the eligibility criteria and provide informed consent will be assigned in a 1:1 ratio to either the MSC intervention group or the control group using a computer-generated random sequence. Sequence generation The random allocation sequence will be created by an independent statistician who is not involved in participant recruitment, assessment, treatment administration, or data analysis. Randomization will be performed using a block randomization method with variable block sizes to maintain group balance throughout the enrollment period. Implementation After confirming eligibility and obtaining informed consent, the study coordinator will assign the participant to the next available allocation according to the concealed randomization list. The person enrolling participants will not have access to the random sequence. Stratification If applicable, randomization may be stratified by key prognostic factors such as: Baseline radiographic severity of knee OA Study center Age group or sex If no stratification is planned, this should be explicitly stated.

This clinical trial utilizes a single-blind design in which the statistical analyst remains blinded to the treatment allocation, while participants, the administering clinician, and the clinical outcome assessors are aware of the intervention. To maintain the integrity of the statistical analysis, the randomization sequence is generated by an independent statistician, and treatment assignments—comprising either Wharton’s jelly–derived mesenchymal stromal cells or high molecular weight Hyaluronic Acid—are allocated to participants upon enrollment. All clinical data, including VAS scores, WOMAC indices, physical examination findings, and adverse events, are recorded and entered into the database by the clinical team without blinding. Prior to statistical evaluation, the data is pseudonymized using neutral group identifiers (e.g., Group 1 and Group 2), ensuring that the data analyst remains blinded to the nature of the interventions during the analysis phase. Unblinding and the subsequent reconciliation of the group identifiers with the actual interventions will occur only after the primary statistical analysis is finalized and the study database is officially locked.