Noorwali Abdulwahab, Aljoud Fadwa, Alghamdi Amani, Sattami Noora, Bashah Taghreed, Noorwali Abdulsalam, Pushparaj Peter Natesan, Gauthaman Kalamegam
Regenerative Medicine Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Scientific Research Center, Dar Al-Hekma University, Jeddah, 22246, Saudi Arabia.
Heliyon. 2024 Oct 29;10(21):e39940. doi: 10.1016/j.heliyon.2024.e39940. eCollection 2024 Nov 15.
Osteoarthritis (OA) is a prevalent joint disorder characterized by joint pain, functional impairment, and disability. The current study investigated the therapeutic effects of intra-articular injection of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) in rats with knee OA.
Fourty five male Wistar rats were randomly divided into three groups (A-C) and received either an intra-articular injection of normal saline (NS) or rBM-MSCs. The normal control group (A, n = 15) received NS, the OA control group (B, n = 15) received NS, and the OA treated group (C, n = 15) received rBM-MSCs (0.5 × 10 cells in 25 μL NS). Knee OA was induced using monosodium iodoacetate (MIA). rBM-MSCs were sourced from female Wistar rats and their stem cells were characterized using flow cytometry. Histomorphometric analyses were performed on knee sections from both normal and OA knee. Serum biomarkers, including hyaluronic acid (HA), cross-linked N-telopeptide of type I collagen-1 (NTX-1), NGF, calcitonin gene-related peptide (CGRP), matrix metalloproteinase-3 (MMP-3), oligomeric cartilage matrix protein COMP, interleukin-6 (IL-6), and soluble IL-6 receptor (sIL-6R), were analyzed using ELISA kits. Ingenuity Pathway Analysis (IPA) was used to determine the genes regulated by MSCs in OA, and the protective mechanisms were determined using the Molecular Activity Predictor (MAP).
rBM-MSCs were positive for CD29 and CD90 and negative for CD45 surface markers. OA biomarkers were significantly elevated in the untreated OA group but decreased after treatment with intra-articular MSCs. The OA group treated with MSCs showed significant repair of the damaged cartilage compared to the control group.
Cartilage damage leads to an increase in inflammatory cytokine levels and is associated with an increase in serum biomarkers related to cartilage degradation. Intra-articular administration of MSCs showed beneficial effects, including regeneration of damaged cartilage and a reduction in inflammation-related serum biomarker levels.
骨关节炎(OA)是一种常见的关节疾病,其特征为关节疼痛、功能障碍和残疾。本研究调查了关节腔内注射大鼠骨髓间充质干细胞(rBM-MSCs)对膝骨关节炎大鼠的治疗效果。
45只雄性Wistar大鼠随机分为三组(A - C组),分别接受关节腔内注射生理盐水(NS)或rBM-MSCs。正常对照组(A组,n = 15)接受NS,骨关节炎对照组(B组,n = 15)接受NS,骨关节炎治疗组(C组,n = 15)接受rBM-MSCs(25μL NS中含0.5×10个细胞)。使用碘乙酸钠(MIA)诱导膝骨关节炎。rBM-MSCs来源于雌性Wistar大鼠,其干细胞通过流式细胞术进行鉴定。对正常膝关节和骨关节炎膝关节切片进行组织形态计量学分析。使用ELISA试剂盒分析血清生物标志物,包括透明质酸(HA)、I型胶原交联N端肽-1(NTX-1)、神经生长因子(NGF)、降钙素基因相关肽(CGRP)、基质金属蛋白酶-3(MMP-3)、寡聚软骨基质蛋白(COMP)、白细胞介素-6(IL-6)和可溶性IL-6受体(sIL-6R)。使用 Ingenuity Pathway Analysis(IPA)确定骨关节炎中受间充质干细胞调节的基因,并使用分子活性预测器(MAP)确定保护机制。
rBM-MSCs的CD29和CD90呈阳性,CD45表面标志物呈阴性。未治疗的骨关节炎组中骨关节炎生物标志物显著升高,但关节腔内注射间充质干细胞治疗后降低。与对照组相比,接受间充质干细胞治疗的骨关节炎组受损软骨有明显修复。
软骨损伤导致炎性细胞因子水平升高,并与软骨降解相关血清生物标志物增加有关。关节腔内给予间充质干细胞显示出有益效果,包括受损软骨再生和炎症相关血清生物标志物水平降低。