مقالات پذیرفته شده در هشتمین کنگره بین المللی زیست پزشکی
Synergistic Effects of Mesenchymal Stem Cells, Hyaluronic Acid and Melatonin on Cartilage Regeneration in a Rat Model of Osteoarthritis
Synergistic Effects of Mesenchymal Stem Cells, Hyaluronic Acid and Melatonin on Cartilage Regeneration in a Rat Model of Osteoarthritis
Seyed Mohammad Hassan Moallem,1Maryam Hashemi,2Sara Amel farzad,3Mohammad Taghi Peivandi,4Zahra Salmasi,5,*
1. Department of Orthopedic department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 2. Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran 3. Pharmaceutical Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran 4. Department of Orthopedic department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 5. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Introduction: Osteoarthritis (OA) as a common joint disorder, affects a great number of people around the world and characterized by the deterioration of articular cartilage and persistent inflammation. Current OA remedies are not quite adequate due to their main focus on pain management and in some cases, have been proven to cause side effects. Intra-articular injection of some treatments such as stem cells or hyaluronic acid (HA) is simple and non-invasive procedure which has emerged as a promising path for cartilage healing. HA injections has been approved by the United States Food and Drug Administration for the purpose of knee OA therapy.
The purpose of the present study was to vet the efficacy of a therapeutic combination of adipose-derived mesenchymal stem cells (AD-MSCs), hyaluronic acid (HA), and melatonin (ME) for cartilage repair in the rat OA model.
Methods: OA were induced in the knee joint of Male Wistar rats by injecting monosodium iodoacetate (MIA) (1 mg of MIA dissolved in 50 μL of saline solution). Normal saline solution was used as a control. Two weeks after the injection, rats were divided into 9 groups (n=7) at random receiving intra-articular knee injections of stem cells, hyaluronic acid and melatonin, as well as various combined treatments. On days 28 and 56, the rats from each group were first selected, weighed, and then subjected to X-ray imaging. The pathological changes in the rats' joints were assessed using the criteria established by Boulocher et al. Then blood samples were taken from the rats and plasma levels of TNF-α and IL-6 were measured. Finally, the rats were anesthetized and euthanized, then, hematoxylin-eosin staining (HE) was used to investigate the changes in pathologic features of knee joint samples.
Results: Radiological evaluations showed that the group treated with MSCs + ME + HA, displayed an appropriate response, with only a slight reduction in joint space and mild osteophytes in one compartment. The group treated with HA +MSCs showed no reduction in joint space and moderate osteophyte in the tibia and osteophyte in the fabula. The overall joint score in the HA+ME and MSC+HA+ME groups was significantly improved compared to the MIA group.
Investigation of TNF and IL-6 plasma levels showed that the group treated with MSC+HA+ME, both on day 28 and day 56, had the lowest amount of TNF-α and IL-6 and this difference with other groups was *** P < 0.001. After that, the MSC+HA group, on days 28 and 56, had the lowest amount of TNF-α and IL-6 compared to other groups.
Pathologic examinations also exhibited significant differences between the treatment groups and the non-treated group, which indicated that these combination therapies can provide a significant improvement in joint pathology (p < 0.05).
Conclusion: These findings indicate that the combination therapy with MSC, HA and ME offers a promising and innovative strategy for OA treatment and can be further investigated for clinical applications.