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Unlocking the Potential Role of Decellularized Biological Scaffolds as a 3D Radiobiological Model for Low- and High-LET Irradiation
by
, , , , , , , , , and
Alexandra Charalampopoulou
1,2,*,†,
Amelia Barcellini
3,4,*,†,
Andrea Peloso
5,
Alessandro Vanoli
6,7,
Stefania Cesari
6,7,
Antonia Icaro Cornaglia
8,
Margarita Bistika
9,
Stefania Croce
10,
Lorenzo Cobianchi
11,12,13,
Giovanni Battista Ivaldi
14,
Laura Deborah Locati
3,15,
Giuseppe Magro
16,
Paola Tabarelli de Fatis
17,
Marco Giuseppe Pullia
18,
Ester Orlandi
4,12 and
Angelica Facoetti
1 1
CNAO National Center for Oncological Hadrontherapy, Radiobiology Unit, Research and Development Department, 27100 Pavia, Italy
2
Hadron Academy PhD Course, School for Advanced Studies (IUSS), 27100 Pavia, Italy
3
Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
4
CNAO National Center for Oncological Hadrontherapy, Radiation Oncology Unit, Clinical Department, 27100 Pavia, Italy
5
Division of Visceral Surgery, Department of Surgery, Geneva University Hospitals, 1205 Geneva, Switzerland
6
Unit of Anatomic Pathology, Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy
7
Unit of Anatomic Pathology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
8
Unit of Histology and Embryology, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy
9
Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy
10
Cell Factory, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
11
Department of General Surgery, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
12
Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
13
Collegium Medicum, University of Social Sciences, 90-419 Łodz, Poland
14
Istituti Clinici Scientific Maugeri IRCCS, Radiation Oncology Department, 27100 Pavia, Italy
15
Medical Oncology Unit, Istituti Clinici Scientific Maugeri IRCCS, 27100 Pavia, Italy
16
CNAO National Center for Oncological Hadrontherapy, Medical Physics Unit, Clinical Department, 27100 Pavia, Italy
17
Medical Physic Unit, Istituti Clinici Scientific Maugeri IRCCS, 27100 Pavia, Italy
18
Research and Development Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work and share the co-first authorship.
Cancers 2024, 16(14), 2582; https://doi.org/10.3390/cancers16142582
Submission received: 16 June 2024
/
Revised: 10 July 2024
/
Accepted: 12 July 2024
/
Published: 18 July 2024
(This article belongs to the Special Issue The Future of Radiation Research in Cancers, 2nd Edition)
Simple Summary
Two-dimensional (2D) models are unable to mimic the intricacies of the reaction in the natural tumor microenvironment to the irradiation, biological and architectural complexity, or dynamic nature of the many tissues. These features can be recreated using a decellularized extracellular matrix (ECM), such as bioscaffolds. We hypothesized that bioscaffolds can be a feasible and effective three-dimensional (3D) model, worthwhile also for radiobiological aims. To test our hypothesis, two cell lines (HMV-II and PANC-1) were seeded in decellularized porcine liver-derived scaffolds and irradiated with carbon ions (high-LET irradiation) and photons (low-LET irradiation). For the first time in the literature, we found that the 3D environment provided by the bioscaffolds was suitable for radiobiological research as well as being cost-effective. This model provides the opportunity to explore the biological consequences of different radiation modalities over prolonged periods of time.
Abstract
Introduction: Decellularized extracellular matrix (ECM) bioscaffolds have emerged as a promising three-dimensional (3D) model, but so far there are no data concerning their use in radiobiological studies. Material and Methods: We seeded two well-known radioresistant cell lines (HMV-II and PANC-1) in decellularized porcine liver-derived scaffolds and irradiated them with both high- (Carbon Ions) and low- (Photons) Linear Energy Transfer (LET) radiation in order to test whether a natural 3D-bioscaffold might be a useful tool for radiobiological research and to achieve an evaluation that could be as near as possible to what happens in vivo. Results: Biological scaffolds provided a favorable 3D environment for cell proliferation and expansion. Cells did not show signs of dedifferentiation and retained their distinct phenotype coherently with their anatomopathological and clinical behaviors. The radiobiological response to high LET was higher for HMV-II and PANC-1 compared to the low LET. In particular, Carbon Ions reduced the melanogenesis in HMV-II and induced more cytopathic effects and the substantial cell deterioration of both cell lines compared to photons. Conclusions: In addition to offering a suitable 3D model for radiobiological research and an appropriate setting for preclinical oncological analysis, we can attest that bioscaffolds seemed cost-effective due to their ease of use, low maintenance requirements, and lack of complex technology
Keywords:
3D model; bioscaffolds; high LET; low LET
