Development of a biomimetic bone on chip to study kidney cancer metastasis : ONCOTRAP - SIS2M
Communication Dans Un Congrès Année : 2024

Development of a biomimetic bone on chip to study kidney cancer metastasis : ONCOTRAP

Résumé

The majority of the solid tumors generate metastasis in different organs like the bone. This late tumor stage is considered as a lethal disease as the patient prognosis is very poor and treatments are partially efficient. In the case of kidney cancer, 30% of patients are metastatic at diagnosis, despite improvements in medical imaging and target therapies. Predicting the evolution of cancer would be helpful for biologists to choose the best therapeutic strategy. Due to unethical issues of animal models and its lack of representation of human tissue behavior, alternatives such as organ-on-chip appear with the potential to study the aggressiveness of metastatic cells and to test anti-metastatic drugs. Unfortunately few bone-on-chip devices have been so far developed [1]. We have designed a metastasis-on-chip to study patient kidney cancer cells invasion towards bone niche. Herein, to recreate a bone niche, we aim to use human Periosteum Derived Stem Cells (hPDSC) that differentiate into osteoblasts in the presence of Bone Morphogenetic Protein 2 (BMP2). BMP2 delivery is usually regulated by extracellular matrix components such as the glycosaminoglycan heparan sulfate (HS). A biomaterial already developed by our team promotes osteogenic differentiation through the interaction HS/BMP2 [2]. The microfluidic chip is made of two main chambers (Figure 1): in chamber1 (Ch1), renal tumoroids are inserted in a collagen 3D matrix [3], in Ch2 hPDSC are differentiated into bone on the biomaterial. A channel with pillars connects the two chambers. Thanks to numerical simulation, we predicted and validated the flow direction of both inlets and found optimized flow rates for cell culture and functionalization of the Ch2 with the biomaterial. We use a counter pressure effect to reduce the risk of molecules diffusion in Ch1. We set up a microfluidic bench based on pressure flow controllers to control precisely in space the functionalization of the biomimetic platform. We have successfully built up, step by step, the biomaterial in only the bone chamber. hPDSCs differentiation to bone is validated with osteogenic differentiation markers such as Osterix and Alkaline Phosphatase. In the next future we will insert the renal tumoroid in the Ch1 to study the cancer invasion.

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Dates et versions

hal-04718061 , version 1 (02-10-2024)

Identifiants

  • HAL Id : hal-04718061 , version 1

Citer

Elisa Lambert, Beatrice Cesana, Catherine Pillet, Joris Kaal, Jules Heraud, et al.. Development of a biomimetic bone on chip to study kidney cancer metastasis : ONCOTRAP. EUROoCS annual meeting, Jul 2024, Milan, Italy. ⟨hal-04718061⟩
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