Research Article Are Stem Cells Derived from Synovium and Fat Pad Able to Treat Induced Knee Osteoarthritis in Rats? Reza Zare, 1 Nader Tanideh , 2,3 Behrooz Nikahval, 1 Maryam Sadat Mirtalebi, 4 Nasrollah Ahmadi, 5 Shahrokh Zarea, 2 Omid Koohi Hosseinabadi, 2 Rohan Bhimani , 6 and Soheil Ashkani-Esfahani 2,6 1 Department of Veterinary Surgery, Shiraz University, Shiraz, Iran 2 Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran 3 Pharmacology Department, Shiraz University of Medical Sciences, Shiraz, Iran 4 Department of Molecular Pathology and Cytogenetic, Shiraz University of Medical Sciences, Shiraz, Iran 5 Department of Veterinary Pathology, Shiraz University, Shiraz, Iran 6 Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA Correspondence should be addressed to Nader Tanideh; tanidehn@gmail.com and Soheil Ashkani-Esfahani; soashkani@gmail.com Received 21 February 2020; Revised 4 June 2020; Accepted 8 June 2020; Published 13 July 2020 Academic Editor: Bruce M. Rothschild Copyright © 2020 Reza Zare et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Osteoarthritis (OA) is a chronic disease and a significant cause of joint pain, tenderness, and limitation of motion. At present, no specific treatment is available, and mesenchymal stem cells (MSCs) have shown promising potentials in this regard. Herein, we aimed to evaluate the repairing potentials of stem cells derived from the synovium and fat pad in the treatment of OA. Methods. Twenty-eight male rats (220 ± 20 g, aged 10-12 weeks), were randomly divided into four groups (n =7): C1: nontreated group, C2: Hyalgan-treated group, E1: adipose tissue-derived stem cell-treated group, and E2: synovial membrane- based stem cell-treated group. Collagenase type II was injected into the left knee; after eight weeks, OA was developed. Then, stem cells were injected, and rats were followed for three months. Afterward, specimens and radiological images were investigated. p value ≤ 0.05 was set as statistically significant. Results. Compared to the C1 group, the E1 and E2 groups showed significantly better results in all six pathological criteria as well as joint space width and osteophytes of medial tibial, medial femoral, and medial fabellar condyles (p ≤ 0:001). Similarly, compared to the C2 group, the E1 and E2 groups had better scores regarding surface, matrix, cell distribution, and cell population viability (p <0:05). E2 showed considerably higher scores compared to C2 regarding subchondral bone and cartilage mineralization (p <0:05). The joint space width was similar between the C2 and E groups. Conclusion. Treatment of OA with MSCs, particularly synovial membrane-derived stem cells, not only prevented but also healed OA of the knee to some extent in comparison to the Hyalgan and nontreatment groups. 1. Introduction Osteoarthritis (OA) is a common joint disorder and one of the leading causes of pain and disability, particularly in the elderly [1]. The epidemiology of this disorder is complex and multifactorial [2]. It is estimated that about 60% of the seniors up to the age of 65 years old present symptoms of OA [3, 4]. The precise pathologic mechanisms leading to the destruction of articular cartilage are unclear. Inadequate mobility may limit sufficient nourishment of the joint through synovial fluid and may lead to cell death [5, 6]. Mediators, such as catabolic cytokines and nitric oxide (NO), interleukin 1 (IL1), and tumor necrosis factor-alpha (TNF-a), modulate the production of destructive enzymes as well as the synthesis of collagen bundles and proteoglycans; these play important roles in the destruction of cartilage struc- tures [5, 6]. Treatment methods of OA may include pharma- cological therapy (i.e., intra-articular therapy, corticosteroids, Hindawi International Journal of Rheumatology Volume 2020, Article ID 9610261, 8 pages https://doi.org/10.1155/2020/9610261