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

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 <i>in vitro</i> 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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Publication Details

Journal
Experimental and Therapeutic Medicine
Published
2024-12-24
DOI
https://doi.org/10.3892/etm.2024.12789
Citations
1
Primary Topic
Cancer Cells and Metastasis
Type
article
Field-Weighted Citation Impact
0.28

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

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1 citations
Experimental and Therapeutic Medicine
Cancer Cells and Metastasis
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article

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

Takamichi Igarashi, Takehiko Yokobori, Kenichiro Araki, Ken Shirabe, Takaomi Seki, Norio Kubo, Akira Watanabe, Ryosuke Fukushima, Ryo Muranushi, Bilguun Erkhem‐Ochir, Norihiro Ishii, Takayuki Okuyama, Kouki Hoshino, Dolgormaa Gantumur, Mariko Tsukagoshi, Haruka Okami, Gendensuren Dorjkhorloo, Takahiro Yamanaka, Kei Hagiwara, Shunsuke Kawai, Hiroshi Saeki
article en
1 citations

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 <i>in vitro</i> 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.

Experimental and Therapeutic MedicineVol. 29(2)
Gunma University (JP)
Fujifilm Corporation, Japan Society for the Promotion of Science
Openalex Percentile: Top 33%
Cancer Cells and Metastasis
0.28
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