3D-bioprinted cancer-on-a-chip: level-up organotypic in vitro models

Monteiro, Maria do Céu; Zhang, Yu Shrike; Gaspar, Vítor M.; Mano, João F.

doi:10.1016/j.tibtech.2021.08.007

Cited by 37 publications

(24 citation statements)

References 128 publications

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“…Further advances for processing tissue-derived ECM and promoting organoids generation have been recently achieved in line with the rapid expansion of 3D bioprinting technologies. [123,124] By exploiting biofabrication techniques stem cells were bioprinted into intestinal-like tissues that comprised structures such as lumens, tubular intestinal epithelia, and branched vasculature networks. Such approach adds supporting cells to the constructs, increasing their complexity.…”

Section: Decm Hydrogels Multi-scale Processabilitymentioning

confidence: 99%

Advancing Tissue Decellularized Hydrogels for Engineering Human Organoids

Moura

Monteiro

Ferreira

et al. 2022

Adv Funct Materials

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The extracellular matrix plays a critical role in bioinstructing cellular self‐assembly and spatial (re)configuration processes that culminate in human organoids in vitro generation and maturation. Considering the importance of the supporting matrix, herein is showcased the most recent advances in the bioengineering of decellularized tissue hydrogels for generating organoids and assembloids. Key design blueprints, characterization methodologies, and extracellular matrix processing toolboxes are comprehensively discussed in light of current advances. Such enabling approaches provide the grounds for engineering next‐generation tissue‐specific hydrogels with close‐to‐native biomolecular signatures and user‐tailored biophysical properties that may potentiate organoids physiomimetic potential. In a forward looking perspective, the combination of tissue‐specific decellularized hydrogels with increasingly complex multicellular assemblies and bottom‐up cell engineering technologies may unravel unprecedented tissue‐like physiological responses and further advance the exploitation of organoids and assembloids as human disease surrogates or as patient‐tailored living therapeutics.

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Section: Decm Hydrogels Multi-scale Processabilitymentioning

confidence: 99%

Advancing Tissue Decellularized Hydrogels for Engineering Human Organoids

Moura

Monteiro

Ferreira

et al. 2022

Adv Funct Materials

Self Cite

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“…Also, PBMCs from a healthy donor were isolated from peripheral blood using Ficoll Paque Plus (GE17-1440-03, Merck, Germany) according to manufacturers' instructions. The 3D bioprinting process was performed using the pneumatic extrusion-based bioprinter Bio X ™ (Cellink, Goteborg, Sweden), as described before (8)(9)(10). Before printing, a cell suspension was created using a 1:1 mixture of PBMCs and patient-derived tumor cells in the respective culture medium.…”

Section: Three-dimensional Patient-derived Tumor Bioprintingmentioning

confidence: 99%

Immune features of the peritumoral stroma in pancreatic ductal adenocarcinoma

et al. 2022

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BackgroundThe peritumoral stroma is a hallmark of pancreatic ductal adenocarcinoma (PDA) with implications for disease development, progression and therapy resistance. We systematically investigated immune features of the stroma in PDA patients to identify markers of clinical importance and potential therapeutic targets.MethodsTissue and blood samples of 51 PDA patients with clinical and follow-up information were included. Laser Capture Microdissection allowed us to analyze the stromal compartment in particular. Systematic immunohistochemistry, followed by software-based image analysis were conducted. Also, multiplex cytokine analyses (including 50 immune-related molecules) were performed. Functional analyses were performed using patient-derived 3D bioprints. Clinical information was used for survival analyses. Intercompartmental IL9 and IL18 gradients were assessed in matched samples of tumor epithelium, stroma, and serum of patients. Serum levels were compared to an age-matched healthy control group.ResultsStromal IL9 and IL18 are significantly associated with patient survival. While IL9 is a prognostic favorable marker (p=0.041), IL18 associates with poor patient outcomes (p=0.030). IL9 correlates with an anti-tumoral cytokine network which connects regulation of T helper (Th) 9, Th1 and Th17 cells (all: p<0.05 and r>0.5). IL18 correlates with a Th1-type cytokine phenotype and stromal CXCL12 expression (all: p<0.05 and r>0.5). Further, IL18 associates with a higher level of exhausted T cells. Inhibition of IL18 results in diminished Th1- and Th2-type cytokines. Patients with high stromal IL9 expression have a tumor-to-stroma IL9 gradient directed towards the stroma (p=0.019). Low IL18 expression associates with a tumor-to-stroma IL18 gradient away from the stroma (p=0.007). PDA patients showed higher serum levels of IL9 than healthy controls while serum IL18 levels were significantly lower than in healthy individuals. The stromal immune cell composition is distinct from the tumor epithelium. Stromal density of FoxP3+ regulatory T cells showed a tendency towards improved patient survival (p=0.071).ConclusionAn unexpected high expression of the cytokines IL9 and IL18 at different ends is of significance in the stroma of PDA and relates to opposing patient outcomes. Sub-compartmental cytokine analyses highlight the importance of a differentiated gradient assessment. The findings suggest stromal IL9 and/or IL18 as markers for patient stratification and as potential therapeutic targets. Future steps include investigating e. g. the role of local microbiota as both cytokines are also regulated by microbial compositions.

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“…Both hiPSCs and hESCs have allowed the study of human cells which are not normally accessible to study in the human body (for example, neurons and glial cells of the human CNS) and, therefore, have boosted the possibilities in medical research employing human cell lines, permitting the study of mechanisms of human development [ 363 , 364 ]; in vitro disease modelling, including in cancer research [ 365 , 366 , 367 ]; in the development of assays and platforms for drug screening campaigns [ 355 , 368 , 369 ]; in patient stratification and in the development of cell replacement strategies [ 355 , 363 ]. The pioneer monolayer cultures gave way to organoids, spheroids, organ-on-a-chip approaches and more recently assembloids, which employ single cell types or a multitude of different cellular types [ 355 , 360 , 370 , 371 , 372 , 373 ]. One such example is the recently developed model of 3D cortico-motor assembloids by Paşca and collaborators, which has brought this technology into a new state of development [ 374 ], allowing the efficient combination of 3D structures analogous to the cerebral cortex and/or the hindbrain/spinal cord with human skeletal muscle spheroids, generating a functional nervous circuit in vitro [ 374 ].…”

Section: Current Challenges and Future Perspectives In Uveal Melanomamentioning

confidence: 99%

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

Lamas

Martel

Nahon-Estève

et al. 2021

Cancers

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Uveal melanoma (UM) is the most common malignant intraocular tumour in the adult population. It is a rare cancer with an incidence of nearly five cases per million inhabitants per year, which develops from the uncontrolled proliferation of melanocytes in the choroid (≈90%), ciliary body (≈6%) or iris (≈4%). Patients initially present either with symptoms like blurred vision or photopsia, or without symptoms, with the tumour being detected in routine eye exams. Over the course of the disease, metastases, which are initially dormant, develop in nearly 50% of patients, preferentially in the liver. Despite decades of intensive research, the only approach proven to mildly control disease spread are early treatments directed to ablate liver metastases, such as surgical excision or chemoembolization. However, most patients have a limited life expectancy once metastases are detected, since there are limited therapeutic approaches for the metastatic disease, including immunotherapy, which unlike in cutaneous melanoma, has been mostly ineffective for UM patients. Therefore, in order to offer the best care possible to these patients, there is an urgent need to find robust models that can accurately predict the prognosis of UM, as well as therapeutic strategies that effectively block and/or limit the spread of the metastatic disease. Here, we initially summarized the current knowledge about UM by compiling the most relevant epidemiological, clinical, pathological and molecular data. Then, we revisited the most important prognostic factors currently used for the evaluation and follow-up of primary UM cases. Afterwards, we addressed emerging prognostic biomarkers in UM, by comprehensively reviewing gene signatures, immunohistochemistry-based markers and proteomic markers resulting from research studies conducted over the past three years. Finally, we discussed the current hurdles in the field and anticipated the future challenges and novel avenues of research in UM.

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3D-bioprinted cancer-on-a-chip: level-up organotypic in vitro models

Cited by 37 publications

References 128 publications

Advancing Tissue Decellularized Hydrogels for Engineering Human Organoids

Advancing Tissue Decellularized Hydrogels for Engineering Human Organoids

Immune features of the peritumoral stroma in pancreatic ductal adenocarcinoma

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

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