The Effectiveness of Stem Cells and Their Secretome and Exosome Derivatives as a Treatment for Osteoarthritis: Systematic Review and Meta-Analysis

Abstract

Introduction: Osteoarthritis (O.A.) has a significant global prevalence and is one of the most common musculoskeletal diseases. O.A. is defined as chronic inflammation that involves the non-specific immune system. The incidence and years lived with disabilities due to O.A. is increasing in most nations. World Health Organization (WHO) reported that about 528 million people worldwide in 2019 lived with O.A. Patients with O.A. were given analgesics using nonsteroidal anti-inflammatory medications (NSAIDs) to relieve the pain. Other non-surgical options for O.A. are intra-articular injections of hyaluronic acid (H.A.) or steroids. In recent decades, mesenchymal stem cells (MSCs) have appeared as a potential treatment for many illnesses, including O.A. They are the most representative adult stem cells and a key form of the stem cell family, implying that MSCs could be very useful in treating O.A. Therefore, this study aims to investigate and compare the effectiveness of stem cells and their secretome and exosome derivatives as a treatment for O.A.
Method: The studies used in this study originated from online databases (PubMed, Science Direct, Cochrane Library, and Google Scholar), which evaluated the outcomes of stem cells and their secretome and exosome derivatives treatment for O.A. The New Castle and Ottawa Scale for Cohort and Cross-Sectional Studies was used to assess the quality of observational studies, and the quality of trials was evaluated using Cochrane's risk of bias (RoB). Quantitative analysis was carried out using mean difference analysis to determine the overall patient survival rate using Review Manager v.5.4 software. Heterogeneity was evaluated using I-squared and t-squared tests. The risk of publication bias was evaluated using a qualitative funnel plot approach.
Result and Discussion: A total of 22 studies with 1037 participants consisting of 613 OA patients and 424 normal participants. Most studies came from the Asian region, especially Korea and China, and were RCTs. The main source of use of stem cells comes from bone marrow and adipose tissue, with the most common administration method being intra-articular injection. The stem cells group outperformed the comparative group in terms of improvement of cartilage regeneration capacity, visual analog score (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) scores after treatment. The quantitative analysis in this study presented a significant overall mean difference between groups from the VAS score and WOMAC (p<0.05), in which the stem cells group showed better improvement than the comparative group.
Conclusion: Stem cell treatment is the most promising for joint tissue regeneration. MSCs are the most promising stem cells because they are straightforward to harvest, multiply effectively, do not induce the formation of tumors, and are highly tolerated by the immune system. In general, MSCs show promising results in treating O.A. patients.