Investigating the Safety and Regenerative Potential of MSC-Derived Secretome Combined With PRGF in Knee Osteoarthritis

NCT ID: NCT07157891

Last Updated: 2025-09-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-10
• Study Completion Date: 2028-12-11

Brief Summary

This Phase I/II randomized clinical trial investigates the safety, feasibility, and early regenerative potential of intra-articular administration of mesenchymal stem cell (MSC)-derived secretome combined with Plasma Rich in Growth Factors (PRGF) in patients with knee osteoarthritis (KOA). The study aims to assess whether this cell-free, biologically enriched therapeutic combination can reduce pain, improve joint function, and promote cartilage repair.

Detailed Description

Osteoarthritis (OA) is a chronic, degenerative joint disease characterized by progressive cartilage degradation, joint space narrowing, subchondral bone remodeling, inflammation, and pain that ultimately impair mobility and quality of life. Current treatment options, including analgesics, corticosteroids, and surgery, offer symptomatic relief but do not halt disease progression or restore joint tissue integrity.

Recent advancements in regenerative medicine have highlighted the therapeutic potential of mesenchymal stem cells (MSCs), particularly adipose-derived MSCs (AD-MSCs) and umbilical cord- derived MSCs (UC-MSCs), due to their robust paracrine activity. Rather than relying solely on cell engraftment, MSCs exert their therapeutic effects primarily through their secretome. These are complex mixtures of cytokines, growth factors, extracellular vesicles (EVs), and exosomes. This secretome can promote cartilage repair, reduce inflammation, and modulate immune responses, all without the risks associated with live cell transplantation.

This prospective, interventional study aims to evaluate the safety, tolerability, and early efficacy of intra-articular administration of MSC-derived secretome combined with Plasma Rich in Growth Factors (PRGF) in patients with mild to moderate symptomatic knee osteoarthritis (Kellgren-Lawrence grade II-III).The secretome will be collected from culture of human ADMSCs and UCMSCs grown in GMP-compliant labs, characterized for sterility, protein content, particle size, and bioactivity prior to administration.

Primary outcomes will include pain reduction assessment and any adverse events via Visual Analog Scale (VAS) and WOMAC index. If there will be adverse events, they will also be checked. Secondary outcomes will include functional improvement, cartilage regeneration (X-ray or MRI assessment), and changes in synovial inflammatory biomarkers (e.g., IL-1β, TNF-α, IL-6, MMP-13).

This study hypothesizes that the cell-free combination of MSC secretome and PRGF will offer regenerative benefits in knee OA, potentially improving joint function and structure while minimizing the risks associated with live cell therapies. Findings from this trial will inform the design of future large-scale studies and support the development of secretome-based regenerative therapies for osteoarthritis.

Conditions

Osteoarthritis (OA); Knee Injury; Cartilage Degeneration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MSC-Derived Secretome

MSC-derived secretome will be administered as intra-articular injections under ultrasound guidance to the affected knee. Injection will be given twice, each after 6 months. Each injection will consist of 2 mL of concentrated MSC-derived secretome.

Group Type: EXPERIMENTAL

MSC-Derived Secretome

Intervention Type: BIOLOGICAL

The secretome will be collected from cultured MSCs under sterile, GMP-compliant conditions and concentrated to retain bioactive molecules. It will be injected into the affected knee under ultrasound guidance.

MSC-Derived Secretome + Autologous PRGF

MSC-derived secretome combined with autologous plasma-rich in growth factors plasma (PRGF) will be administered as intra-articular injections under ultrasound guidance to the affected knee. Injections will be given twice, each after 6 months. Each injection will consist of 2 mL of concentrated MSC-derived secretome and 1 mL of autologous PRGF, totaling 3 mL per dose.

Group Type: EXPERIMENTAL

MSC-Derived Secretome + Autologous PRGF

Intervention Type: BIOLOGICAL

MSC-derived secretome will be collected from mesenchymal stem cell cultures under sterile, GMP-compliant conditions. Autologous PRP will be prepared from the participant's own peripheral blood using a standardized single-spin centrifugation method and combined with 10% calcium chloride to activate growth factors. Both components will be mixed and administered into the affected joint under ultrasound guidance.

Interventions

MSC-Derived Secretome

The secretome will be collected from cultured MSCs under sterile, GMP-compliant conditions and concentrated to retain bioactive molecules. It will be injected into the affected knee under ultrasound guidance.

Intervention Type: BIOLOGICAL

MSC-Derived Secretome + Autologous PRGF

MSC-derived secretome will be collected from mesenchymal stem cell cultures under sterile, GMP-compliant conditions. Autologous PRP will be prepared from the participant's own peripheral blood using a standardized single-spin centrifugation method and combined with 10% calcium chloride to activate growth factors. Both components will be mixed and administered into the affected joint under ultrasound guidance.

Intervention Type: BIOLOGICAL

Other Intervention Names

Conditioned Medium; MSC Secretome Therapy; MSC-Secretome/PRGF Combined Therapy

Eligibility Criteria

Inclusion Criteria

• Diagnosed with primary OA in one or both knees based on American College of Rheumatology criteria
• Grade I and II Arthritis
• Joint pain ≥ 20mm measured by visual analogue scale
• Age ranges from 30-55 years of age
• BMI 27.12 ± 4.38
• Patients with no previous surgical interventions to lower limb
• Willing to participate in the study

Exclusion Criteria

• • Secondary OA due to trauma, infection, rheumatoid arthritis, congenital disease or other inflammatory disorders of the knee

• Diagnosed with a systemic autoimmune disorder, immunodeficiency or coagulation disorder
• Had history of malignancy
• History of allergy or allergic constitution
• Pregnant or breastfeeding women.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore.

UNKNOWN

Sponsor Role: collaborator

University of the Punjab

OTHER

Sponsor Role: lead

Responsible Party

Noreen Latief

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

MSCSEC-OA-001

Identifier Type: -

Identifier Source: org_study_id