Multiple myeloma (MM) is a malignancy of plasma cells accounting for ≈12% of hematological malignancies. In this study, the fabrication of a high-content in vitro MM model using a coaxial extrusion bioprinting method is reported, allowing formation of a human bone marrow-like microenvironment featuring an outer mineral-containing sheath and the inner soft hydrogel-based core. MM cells are mono-cultured or co-cultured with HS5 stromal cells that can release interleukin-6 (IL-6), where the cells show superior behaviors and responses to bortezomib in 3D models than in the planar cultures. Tocilizumab, a recombinant humanized anti-IL-6 receptor (IL-6R), is investigated for its efficacy to enhance the chemosensitivity of bortezomib on MM cells cultured in the 3D model by inhibiting IL-6R. More excitingly, in a proof-of-concept demonstration, it is revealed that patient-derived MM cells can be maintained in 3D-bioprinted microenvironment with decent viability for up to 7 days evaluated, whereas they completely die off in planar culture as soon as 5 days. In conclusion, a 3D-bioprinted MM model is fabricated to emulate some characteristics of the human bone marrow to promote growth and proliferation of the encapsulated MM cells, providing new insights for MM modeling, drug development, and personalized therapy in the future.

中文翻译：

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3D 生物打印的多发性骨髓瘤模型

多发性骨髓瘤 (MM) 是一种浆细胞恶性肿瘤，约占血液系统恶性肿瘤的 12%。在这项研究中，报道了使用同轴挤压生物打印方法制造高含量的体外 MM 模型，从而形成具有外层含矿物质鞘和内层软水凝胶核心的类骨髓微环境。MM 细胞与可释放白细胞介素 6 (IL-6) 的 HS5 基质细胞进行单一培养或共培养，其中细胞在 3D 模型中表现出优于平面培养的行为和对硼替佐米的反应。Tocilizumab 是一种重组人源化抗 IL-6 受体 (IL-6R)，正在研究其通过抑制 IL-6R 增强硼替佐米对 3D 模型中培养的 MM 细胞的化学敏感性的功效。更令人兴奋的是，在概念验证演示中，经评估，源自患者的 MM 细胞可以在 3D 生物打印微环境中维持长达 7 天，并具有良好的生存能力，而它们在平面培养中最快 5 天就会完全死亡。总之，制造了一个 3D 生物打印的 MM 模型来模拟人类骨髓的一些特征，以促进封装的 MM 细胞的生长和增殖，为未来的 MM 建模、药物开发和个性化治疗提供新的见解。