Human collagen type I‑based scaffold retains human‑derived fibroblasts in a patient‑derived tumor xenograft mouse model

基于人类 I 型胶原蛋白的支架可在患者来源的肿瘤异种移植小鼠模型中保留人类来源的成纤维细胞

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作者:Haruka Okami, Ryo Muranushi, Takehiko Yokobori, Bilguun Erkhem-Ochir, Gendensuren Dorjkhorloo, Takaomi Seki, Takayuki Okuyama, Ryousuke Fukushima, Shunsuke Kawai, Kouki Hoshino, Gantumur Dolgormaa, Kei Hagiwara, Takahiro Yamanaka, Norihiro Ishii, Mariko Tsukagoshi, Takamichi Igarashi, Akira Watanabe

Abstract

The present study aimed to investigate the role of a recombinant protein based on human collagen type I (RCPhC1) as a scaffold in maintaining the human tumor microenvironment within a patient-derived tumor xenograft (PDTX) model. RCPhC1, synthesized under animal component-free conditions, was explored for its potential to support the human-specific stroma associated with tumor growth. PDTX models were established using resected colorectal cancer liver metastasis specimens, and stromal cell populations from humans and mice were compared using three scaffolds: No scaffold (control), Matrigel and recombinant human collagen type I, across two passages. Specific antibodies for human Lamin B and mouse Lamin B were used for immunostaining to distinguish between human and mouse cells. Additionally, the impact of each scaffold on the invasive ability of mouse fibroblasts was assessed using an invasion assay. Patient-derived tumor tissues embedded with RCPhC1 hydrogels had significantly more human Lamin B-positive cells and fewer mouse Lamin B cells than those embedded with no scaffolds or Matrigel. The human Lamin B-positive cells in PDTX tumors with RCPhC1 hydrogels were recognized as fibroblasts. Additionally, these hydrogels significantly reduced the invasion of mouse fibroblast cell lines in vitro compared with Matrigel. The present study investigated RCPhC1 hydrogels as a new scaffold material for tumor engraftment in PDTX mouse models, and identified a promising experimental tool for maintaining the tumor microenvironment.

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