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

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

doi:10.3892/etm.2024.12789

February-2025 Volume 29 Issue 2

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February-2025 Volume 29 Issue 2

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Article Open Access

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

Authors:
- 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
- Norio Kubo
- Kenichiro Araki
- Hiroshi Saeki
- Ken Shirabe
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Affiliations: Department of General Surgical Science, Division of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research, Maebashi, Gunma 371‑8511, Japan, Department of General Surgical Science, Division of Gastroenterological Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan

Copyright: © Okami et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 39
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Published online on: December 24, 2024

https://doi.org/10.3892/etm.2024.12789
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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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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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