Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, 263 Farmington Ave, Farmington, CT, 06030, USA.
Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, USA.
Sci Rep. 2020 Oct 30;10(1):18751. doi: 10.1038/s41598-020-75921-w.
Inflammation leads to chondrocyte senescence and cartilage degeneration, resulting in osteoarthritis (OA). Adipose-derived stem cells (ADSCs) exert paracrine effects protecting chondrocytes from degenerative changes. However, the lack of optimum delivery systems for ADSCs limits its use in the clinic. The use of extracellular matrix based injectable hydrogels has gained increased attention due to their unique properties. In the present study, we developed hydrogels from amnion tissue as a delivery system for ADSCs. We investigated the potential of amnion hydrogel to maintain ADSC functions, the synergistic effect of AM with ADSC in preventing the catabolic responses of inflammation in stimulated chondrocytes. We also investigated the role of Wnt/β-catenin signaling pathway in IL-1β induced inflammation in chondrocytes and the ability of AM-ADSC to inhibit Wnt/β-catenin signaling. Our results showed that AM hydrogels supported cell viability, proliferation, and stemness. ADSCs, AM hydrogels and AM-ADSCs inhibited the catabolic responses of IL-1β and inhibited the Wnt/β-catenin signaling pathway, indicating possible involvement of Wnt/β-catenin signaling pathways in IL-1β induced inflammation. The results also showed that the synergistic effect of AM-ADSCs was more pronounced in preventing catabolic responses in activated chondrocytes. In conclusion, we showed that AM hydrogels can be used as a potential carrier for ADSCs, and can be developed as a potential therapeutic agent for treating OA.
炎症导致软骨细胞衰老和软骨退化，从而导致骨关节炎（OA）。脂肪来源的干细胞（ADSCs）发挥旁分泌作用，保护软骨细胞免受退行性变化。然而，ADSCs 的最佳输送系统的缺乏限制了其在临床上的应用。基于细胞外基质的可注射水凝胶由于其独特的性质而受到越来越多的关注。在本研究中，我们开发了一种源自羊膜组织的水凝胶作为 ADSC 的输送系统。我们研究了羊膜水凝胶维持 ADSC 功能的潜力，AM 与 ADSC 协同预防炎症刺激的软骨细胞分解代谢反应的作用。我们还研究了 Wnt/β-catenin 信号通路在 IL-1β 诱导的软骨细胞炎症中的作用，以及 AM-ADSC 抑制 Wnt/β-catenin 信号通路的能力。我们的结果表明，AM 水凝胶支持细胞活力、增殖和干性。ADSCs、AM 水凝胶和 AM-ADSCs 抑制了 IL-1β 的分解代谢反应，并抑制了 Wnt/β-catenin 信号通路，表明 Wnt/β-catenin 信号通路可能参与了 IL-1β 诱导的炎症。结果还表明，AM-ADSCs 的协同作用在预防激活的软骨细胞的分解代谢反应中更为明显。总之，我们表明 AM 水凝胶可用作 ADSC 的潜在载体，并可开发为治疗 OA 的潜在治疗剂。
