Cell Therapy Research Center, Green Cross LabCell, 107, Ihyeon-ro 30 beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, 16924, South Korea.
Tissue Eng Regen Med. 2021 Oct;18(5):851-862. doi: 10.1007/s13770-021-00350-3. Epub 2021 Jun 11.
Stem cell therapies can be a new therapeutic strategy that may rebalance anabolic and anti-resorptive effects in osteoporosis patients. Tonsil-derived mesenchymal stem cells (TMSCs) can be an alternative therapeutic source for chronic degenerative diseases including osteoporosis. MSCs acquire immune regulatory function under the inflammatory cytokines. Since interleukin (IL) 1β is known to be one of inflammatory cytokines involved in osteoporosis progression, treatment of IL1β with TMSCs may enhance immunomodulatory function and therapeutic effects of TMSCs in osteoporosis.
For IL1β priming, TMSCs were cultured in the presence of the medium containing IL1β for 1 day. Characteristics of IL1β priming TMSCs such as multipotent differentiation properties, anti-inflammatory potential, and suppression of osteoclast differentiation were assessed in vitro. For in vivo efficacy study, IL1β priming TMSCs were intravenously infused twice with ovariectomized (OVX) osteoporosis mouse model, and blood serum and bone parameters from micro computed tomography images were analyzed.
IL1β priming TMSCs had an enhanced osteogenic differentiation and secreted factors that regulate both osteoclastogenesis and osteoblastogenesis. IL1β priming TMSCs also suppressed proliferation of peripheral blood mononuclear cells (PBMCs) and decreased expression of Receptor activator of nuclear factor kappa-Β ligand (RANKL) in PHA-stimulated PBMCs. Furthermore, osteoclast specific genes such as Nuclear factor of activated T cells c1 (NFATc1) were effectively down regulated when co-cultured with IL1β priming TMSCs in RANKL induced osteoclasts. In OVX mice, IL1β priming TMSCs induced low level of serum RANKL/osteoprotegerin (OPG) ratio on the first day of the last administration. Four weeks after the last administration, bone mineral density and serum Gla-osteocalcin were increased in IL1β priming TMSC-treated OVX mice. Furthermore, bone formation and bone resorption markers that had been decreased in OVX mice with low calcium diet were recovered by infusion of IL1β priming TMSCs.
IL1β priming can endow constant therapeutic efficacy with TMSCs, which may contribute to improve bone density and maintain bone homeostasis in postmenopausal osteoporosis. Therefore, IL1β priming TMSCs can be a new therapeutic option for treating postmenopausal osteoporosis.
干细胞疗法可能是一种新的治疗策略，可以重新平衡骨质疏松症患者的合成代谢和抗吸收作用。扁桃体间充质干细胞（TMSCs）可以作为治疗包括骨质疏松症在内的慢性退行性疾病的替代治疗来源。在炎症细胞因子的作用下，间充质干细胞获得免疫调节功能。由于白细胞介素（IL）1β 是已知参与骨质疏松症进展的炎症细胞因子之一，因此用 TMSCs 治疗 IL1β 可能会增强 TMSCs 的免疫调节功能和治疗骨质疏松症的效果。
为了进行 IL1β 预刺激，将 TMSCs 在含有 IL1β 的培养基中培养 1 天。在体外评估 IL1β 预刺激 TMSCs 的多能分化特性、抗炎潜力和抑制破骨细胞分化的能力。在体内疗效研究中，将 IL1β 预刺激 TMSCs 两次静脉内输注到去卵巢（OVX）骨质疏松症小鼠模型中，并分析血清和微计算机断层扫描图像中的骨参数。
IL1β 预刺激 TMSCs 具有增强的成骨分化能力，并分泌调节破骨细胞和成骨细胞生成的因子。IL1β 预刺激 TMSCs 还抑制了外周血单核细胞（PBMCs）的增殖，并降低了 PHA 刺激的 PBMCs 中核因子κB 受体激活剂配体（RANKL）的表达。此外，当与 IL1β 预刺激 TMSCs 共培养时，核因子激活 T 细胞 c1（NFATc1）等破骨细胞特异性基因在 RANKL 诱导的破骨细胞中被有效下调。在 OVX 小鼠中，IL1β 预刺激 TMSCs 在最后一次给药的第一天诱导低水平的血清 RANKL/骨保护素（OPG）比值。最后一次给药后 4 周，IL1β 预刺激 TMSC 处理的 OVX 小鼠的骨矿物质密度和血清 Gla-骨钙素增加。此外，用 IL1β 预刺激 TMSCs 输注可恢复低钙饮食 OVX 小鼠中降低的骨形成和骨吸收标志物。
IL1β 预刺激可以赋予 TMSCs 持续的治疗效果，这可能有助于改善绝经后骨质疏松症患者的骨密度并维持骨稳态。因此，IL1β 预刺激 TMSCs 可以作为治疗绝经后骨质疏松症的新治疗选择。
