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芯片上的骨髓瘤模型模仿瘤内异质性,以探讨与瘤相关的巨细胞重编程,用于免疫疗法

Chitra Jaiswal¹, Saki Sugihara¹, Souradeep Dey²

¹Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati-781 039, Assam, India.

|December 23, 2025

概括

研究人员开发了一种新的骨髓瘤瘤微环境 (OS-TME) 3D模型,以研究免疫细胞相互作用. 这种模型成功地将促进瘤的巨细胞重新编程为抑制瘤的表型,为骨髓瘤提供了新的治疗策略.

科学领域:

生物医学工程生物医学工程
癌症研究癌症研究
免疫学免疫学免疫学

背景情况:

骨髓瘤瘤微环境 (OS-TME) 是复杂的,免疫细胞如瘤相关巨细胞 (TAMs) 和机械压力影响进展.
向TAM是一种有前途的策略,可以改善骨髓瘤治疗结果.

研究的目的:

开发和验证一种新的免疫能力高的三种培养骨肉瘤 (iTC-OS) 模型.
使用微流体生物反应器,研究在模拟的OS-TME中对TAM的重新编程.

主要方法:

创建了一个 3D SF-HA 脚手架模型,其中包含 OS 细胞, TAM 和 HUVEC.
将iTC-OS模型集成到具有动态 perfusion 的微流体生物反应器 (iTC-OS-on-a-chip) 中.
使用pexidartinib和tenalisib分别抑制CSF1R和PI3Kγ,以评估TAM重编程.
通过ELISA通过基因表达和细胞因子分泌分析了M1/M2巨标记物.

主要成果:

芯片上的iTC-OS模型成功模拟了瘤内机械应力梯度.
对CSF1R和PI3Kγ的药理抑制有效地将M2 TAM重编程为M1表型.
基因表达和细胞因子分析证实了TAMs从M2重编程到M1.

结论:

开发的iTC-OS-on-a-chip模型为研究OS-免疫相互作用提供了一个生理相关的平台.
这种模型有助于对骨髓瘤的免疫治疗药物的临床前评估.
这些发现支持TAM重编程作为骨髓瘤的可行治疗策略.

关键词:

药物查是指对药物进行查.瘤内异质性在瘤内异质性大细胞重编程的重编程微流体学微流体学骨质肉瘤骨质肉瘤是什么

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