3D Bioprinted cancer models: Revolutionizing personalized cancer therapy

Augustine, Robin; Kalva, Sumama Nuthana; Ahmad, Rashid; Zahid, Alap Ali; Hasan, Shajia; Nayeem, Ajisha; McClements, Lana

doi:10.1016/j.tranon.2021.101015

Cited by 129 publications

(96 citation statements)

References 206 publications

(153 reference statements)

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“…In the present work, we tested for the first time whether 3D bioprinting strategy could be applied to immune cells and in particular to leukemic B cells. This strategy is currently successfully explored for other cancers such as breast, brain, skin and pancreatic (18). In solid tumors, researching the need to develop in vitro models with a 3D structure recapitulating in vivo tumor growth was more obvious, while this need was appreciated much later in hematological cancer, due to the circulating nature of most diseases (2,3).…”

Section: Discussionmentioning

confidence: 99%

“…Lately, relevant technological advancements have been achieved and have started being applied in biomedicine. One of the most striking is the implementation of 3D bioprinting in biomedical research, which, to date, is considered a very promising approach to generate complex and advanced 3D in vitro models ( 17 , 18 ). Specifically, 3D bioprinting is an additive manufacturing technique in which cells are encapsulated (avoiding cell seeding limitations) within a “bioink” that ideally mimics the native extracellular matrix (ECM), and are subsequently deposited in a layer-by-layer process to a previously defined geometry ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

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3D Bioprinting Allows the Establishment of Long-Term 3D Culture Model for Chronic Lymphocytic Leukemia Cells

et al. 2021

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Chronic Lymphocytic Leukemia (CLL) represents the most common leukemia in the western world and remains incurable. Leukemic cells organize and interact in the lymphoid tissues, however what actually occurs in these sites has not been fully elucidated yet. Studying primary CLL cells in vitro is very challenging due to their short survival in culture and also to the fact that traditional two-dimensional in vitro models lack cellular and spatial complexity present in vivo. Based on these considerations, we exploited for the first time three-dimensional (3D) bioprinting to advance in vitro models for CLL. This technology allowed us to print CLL cells (both primary cells and cell lines) mixed with the appropriate, deeply characterized, hydrogel to generate a scaffold containing the cells, thus avoiding the direct cell seeding onto a precast 3D scaffold and paving the way to more complex models. Using this system, we were able to efficiently 3D bioprint leukemic cells and improve their viability in vitro that could be maintained up to 28 days. We monitored over time CLL cells viability, phenotype and gene expression, thus establishing a reproducible long-term 3D culture model for leukemia. Through RNA sequencing (RNAseq) analysis, we observed a consistent difference in gene expression profile between 2D and 3D samples, indicating a different behavior of the cells in the two different culture settings. In particular, we identified pathways upregulated in 3D, at both day 7 and 14, associated with immunoglobulins production, pro-inflammatory molecules expression, activation of cytokines/chemokines and cell-cell adhesion pathways, paralleled by a decreased production of proteins involved in DNA replication and cell division, suggesting a strong adaptation of the cells in the 3D culture. Thanks to this innovative approach, we developed a new tool that may help to better mimic the physiological 3D in vivo settings of leukemic cells as well as of immune cells in broader terms. This will allow for a more reliable study of the molecular and cellular interactions occurring in normal and neoplastic conditions in vivo, and could also be exploited for clinical purposes to test individual responses to different drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

3D Bioprinting Allows the Establishment of Long-Term 3D Culture Model for Chronic Lymphocytic Leukemia Cells

et al. 2021

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“…Recent progress in bioprinting enables the development of 3D in vitro models of various kinds of cancerous tissue [220]. Such models enable the design of patient-specific therapies as well as for the investigation of the processes related to carcinogenesis, such as tumor extravasation [221].…”

Section: Cancer Modelsmentioning

confidence: 99%

Advances in 3D Printing for Tissue Engineering

et al. 2021

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Tissue engineering (TE) scaffolds have enormous significance for the possibility of regeneration of complex tissue structures or even whole organs. Three-dimensional (3D) printing techniques allow fabricating TE scaffolds, having an extremely complex structure, in a repeatable and precise manner. Moreover, they enable the easy application of computer-assisted methods to TE scaffold design. The latest additive manufacturing techniques open up opportunities not otherwise available. This study aimed to summarize the state-of-art field of 3D printing techniques in applications for tissue engineering with a focus on the latest advancements. The following topics are discussed: systematics of the available 3D printing techniques applied for TE scaffold fabrication; overview of 3D printable biomaterials and advancements in 3D-printing-assisted tissue engineering.

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“…Bioprinted cell models are innovative platforms that enable the deposition of bioinks containing multiple types of living cells, signaling molecules, decellularized extracellular matrix constituents, nutrients, growth factors, and cell-laden biomaterials using a computeraided design (CAD) in order to engineer 3D constructs with tissue-like architecture [98,104]. According to their origin, bioprinting materials vary from natural polymers such as alginate, gelatin, collagen, fibrin, and hyaluronic acid-based to synthetic materials [104].…”

Section: Bioprinted and 3d-printed Hcc Modelsmentioning

confidence: 99%

Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

Blidișel

Marcovici

Coricovac

et al. 2021

Cancers

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Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

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3D Bioprinted cancer models: Revolutionizing personalized cancer therapy

Cited by 129 publications

References 206 publications

3D Bioprinting Allows the Establishment of Long-Term 3D Culture Model for Chronic Lymphocytic Leukemia Cells

3D Bioprinting Allows the Establishment of Long-Term 3D Culture Model for Chronic Lymphocytic Leukemia Cells

Advances in 3D Printing for Tissue Engineering

Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

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