Li Chuncai, Liu Yincong, Deng Mingxing, Li Jun, Li Shengqi, Li Xiaoyu, Zuo Yuling, Shen Chongyang, Wang Yichao
Stem Cells Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
TCM Hospital of Sichuan Province, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Front Pharmacol. 2024 Mar 27;15:1349199. doi: 10.3389/fphar.2024.1349199. eCollection 2024.
Osteoporosis is a systemic bone disease characterized by bone loss and microstructural degeneration. Recent preclinical and clinical trials have further demonstrated that the transplantation of mesenchymal stem cells (MSCs) derived from human adipose tissue (AD), dental pulp (DP), placental amniotic membrane (AM), and umbilical cord (UC) tissues can serve as an effective form of cell therapy for osteoporosis. However, MSC-mediated osteoimmunology and the ability of these cells to regulate osteoclast-osteoblast differentiation varies markedly among different types of MSCs. In this study, we investigated whether transplanted allogeneic MSCs derived from AD, DP, AM, and UC tissues were able to prevent osteoporosis in an ovariectomy (OVX)-induced mouse model of osteoporosis. The homing and immunomodulatory ability of these cells as well as their effects on osteoblastogenesis and the maintenance of bone formation were compared for four types of MSCs to determine the ideal source of MSCs for the cell therapy-based treatment of OVX-induced osteoporosis. The bone formation and bone resorption ability of these four types of MSCs were analyzed using micro-computed tomography analyses and histological staining. In addition, cytokine array-based analyses of serological markers and bioluminescence imaging assays were employed to evaluate cell survival and homing efficiency. Immune regulation was determined by flow cytometer assay to reflect the mechanisms of osteoporosis treatment. These analyses demonstrated that MSCs isolated from different tissues have the capacity to treat osteoporosis when transplanted . Importantly, DP-MSCs infusion was able to maintain trabecular bone mass more efficiently with corresponding improvements in trabecular bone volume, mineral density, number, and separation. Among the tested MSC types, DP-MSCs were also found to exhibit greater immunoregulatory capabilities, regulating the Th17/Treg and M1/M2 ratios. These data thus suggest that DP-MSCs may represent an effective tool for the treatment of osteoporosis.
骨质疏松症是一种以骨质流失和微结构退化为特征的全身性骨病。最近的临床前和临床试验进一步表明，源自人脂肪组织（AD）、牙髓（DP）、胎盘羊膜（AM）和脐带（UC）组织的间充质干细胞（MSC）移植可作为治疗骨质疏松症的一种有效细胞疗法。然而，不同类型的MSC之间，MSC介导的骨免疫学以及这些细胞调节破骨细胞-成骨细胞分化的能力存在显著差异。在本研究中，我们调查了源自AD、DP、AM和UC组织的异体MSC移植是否能够在卵巢切除（OVX）诱导的骨质疏松症小鼠模型中预防骨质疏松症。比较了这四种类型MSC的归巢和免疫调节能力，以及它们对成骨细胞生成和骨形成维持的影响，以确定基于细胞疗法治疗OVX诱导的骨质疏松症的理想MSC来源。使用微计算机断层扫描分析和组织学染色分析这四种类型MSC的骨形成和骨吸收能力。此外，采用基于细胞因子阵列的血清学标志物分析和生物发光成像测定来评估细胞存活和归巢效率。通过流式细胞仪测定确定免疫调节，以反映骨质疏松症的治疗机制。这些分析表明，从不同组织分离的MSC移植时具有治疗骨质疏松症的能力。重要的是，输注DP-MSC能够更有效地维持小梁骨量，同时小梁骨体积、矿物质密度、数量和间距也相应改善。在测试的MSC类型中，还发现DP-MSC表现出更强的免疫调节能力，可调节Th17/Treg和M1/M2比率。因此，这些数据表明DP-MSC可能是治疗骨质疏松症的有效工具。
