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PDX-Derived Ewing’s Sarcoma Cells Retain High Viability and Disease Phenotype in Alginate Encapsulated Spheroid Cultures

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iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal
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Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal
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Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Institut de Recerca Sant Joan de Déu, Passeig Sant Joan de Déu 2, 08950 Barcelona, Spain
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NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain
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Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain
*
Author to whom correspondence should be addressed.
Academic Editors: Teresa Puig Miquel and Joaquim Ciurana Gay
Cancers 2021, 13(4), 879; https://doi.org/10.3390/cancers13040879
Received: 13 January 2021 / Revised: 29 January 2021 / Accepted: 15 February 2021 / Published: 19 February 2021
(This article belongs to the Special Issue Three-Dimensional Culture Systems in Cancer Research)
Ewing’s Sarcoma (ES) is the second most frequent bone tumour in children and young adults, with very aggressive behaviour and significant disease recurrence. To better study the disease and find new therapies, experimental models are needed. Recently, patient-derived xenografts (PDX), obtained by implanting patient tumour samples in immunodeficient mice, have been developed. However, when ES cells are extracted from the patient’s tumour or from PDX and placed on plasticware surfaces, they lose their original 3D configuration, cell identity and function. To overcome these issues, we implemented cultures of PDX-derived ES cells, by making them aggregate to form ES cell spheroids and then encapsulating these 3D spheroids into a hydrogel, alginate, to stabilize the culture. We show that this methodology maintained ES cell viability and intrinsic characteristics of the original ES tumour cells for at least one month and that it is suitable for study the effect of anticancer drugs.
Ewing’s Sarcoma (ES) is the second most frequent malignant bone tumour in children and young adults and currently only untargeted chemotherapeutic approaches and surgery are available as treatment, although clinical trials are on-going for recently developed ES-targeted therapies. To study ES pathobiology and develop novel drugs, established cell lines and patient-derived xenografts (PDX) are the most employed experimental models. Nevertheless, the establishment of ES cell lines is difficult and the extensive use of PDX raises economic/ethical concerns. There is a growing consensus regarding the use of 3D cell culture to recapitulate physiological and pathophysiological features of human tissues, including drug sensitivity. Herein, we implemented a 3D cell culture methodology based on encapsulation of PDX-derived ES cell spheroids in alginate and maintenance in agitation-based culture systems. Under these conditions, ES cells displayed high proliferative and metabolic activity, while retaining the typical EWSR1-FLI1 chromosomal translocation. Importantly, 3D cultures presented reduced mouse PDX cell contamination compared to 2D cultures. Finally, we show that these 3D cultures can be employed in drug sensitivity assays, with results similar to those reported for the PDX of origin. In conclusion, this novel 3D cell culture method involving ES-PDX-derived cells is a suitable model to study ES pathobiology and can assist in the development of novel drugs against this disease, complementing PDX studies. View Full-Text
Keywords: Ewing’s Sarcoma; PDX-derived cells; tumour spheroids; 3D cultures; alginate; drug assays Ewing’s Sarcoma; PDX-derived cells; tumour spheroids; 3D cultures; alginate; drug assays
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MDPI and ACS Style

Domenici, G.; Eduardo, R.; Castillo-Ecija, H.; Orive, G.; Montero Carcaboso, Á.; Brito, C. PDX-Derived Ewing’s Sarcoma Cells Retain High Viability and Disease Phenotype in Alginate Encapsulated Spheroid Cultures. Cancers 2021, 13, 879. https://doi.org/10.3390/cancers13040879

AMA Style

Domenici G, Eduardo R, Castillo-Ecija H, Orive G, Montero Carcaboso Á, Brito C. PDX-Derived Ewing’s Sarcoma Cells Retain High Viability and Disease Phenotype in Alginate Encapsulated Spheroid Cultures. Cancers. 2021; 13(4):879. https://doi.org/10.3390/cancers13040879

Chicago/Turabian Style

Domenici, Giacomo, Rodrigo Eduardo, Helena Castillo-Ecija, Gorka Orive, Ángel Montero Carcaboso, and Catarina Brito. 2021. "PDX-Derived Ewing’s Sarcoma Cells Retain High Viability and Disease Phenotype in Alginate Encapsulated Spheroid Cultures" Cancers 13, no. 4: 879. https://doi.org/10.3390/cancers13040879

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