Macrophages are the most abundant immune cells in the microenvironment of solid tumors. The present study displayed histological and immunohistochemical analyses of a malignant tumor model developed from cancer stem cells (CSCs) converted from human induced pluripotent stem cells (hiPSCs) in a cancer microenvironment prepared from the conditioned medium (CM) of a pancreatic cancer cell line. We focused on the localization and the origin of tumor-associated macrophages (TAMs), To the best of our knowledge this may be the first study to suggest the potential differentiation of CSCs to TAMs.

hiPSCs were converted into CSCs in the presence of CM from PK8 cells. CSCs were then transplanted in vivo and formed primary tumors. Primary cultures for these tumors were serially transplanted again to obtain secondary tumors. Secondary tumors exhibited histopathological features of malignancy. Cells derived from tumors maintained the expression of endogenous stemness markers and pancreatic CSCs markers. Simultaneously, high immunoreactivity to anti-mouse CD68, anti-human CD68, CD206 and CD11b antibodies were detected revealing that the tumor tissue derived from CSCs was enriched for macrophages which can originate from both human and mouse cells.

The model of CSCs highlighted the possibility of CSCs to differentiate into TAMs.

巨噬细胞是实体瘤微环境中含量最丰富的免疫细胞。本研究展示了从胰腺癌细胞系的条件培养基 (CM) 制备的癌症微环境中由人类诱导多能干细胞 (hiPSCs) 转化而来的癌症干细胞 (CSCs) 开发的恶性肿瘤模型的组织学和免疫组织化学分析。我们专注于肿瘤相关巨噬细胞 (TAM) 的定位和起源，据我们所知，这可能是第一项表明 CSCs 可能向 TAMs 分化的研究。

在来自 PK8 细胞的 CM 存在下，hiPSCs 被转化为 CSCs。然后将 CSC 移植到体内并形成原发肿瘤。这些肿瘤的原代培养物再次连续移植以获得继发性肿瘤。继发性肿瘤表现出恶性肿瘤的组织病理学特征。源自肿瘤的细胞保持内源性干细胞标志物和胰腺 CSCs 标志物的表达。同时，检测到对抗小鼠 CD68、抗人 CD68、CD206 和 CD11b 抗体的高免疫反应性，表明来源于 CSC 的肿瘤组织富含巨噬细胞，巨噬细胞可以来源于人和小鼠细胞。

CSCs 模型强调了 CSCs 分化为 TAMs 的可能性。