Optimizing P3D Scaffolds bone tumor models for research on metastases to bone

Particle3D is happy to welcome our new research intern, Rie Andersen Lassen, who will be engaging in a new research project to optimize P3D Scaffolds based tumor models for research in metastases to bone. That is, the spread of cancer cells from cancerous tumors to bone.

Below, you can read how Rie describes her project.

 

The aim of this project is to optimize the P3D Scaffold for application in the field of bone metastases research to construct in vitro models suitable as replacements for in vivo studies to reduce animal harm and study costs. The optimization will be focused on improving the composition of the P3D Scaffolds’ components and structure, paired with human mesenchymal stem cells (hMSCs) to construct a “base” scaffold that exhibit traits and transmitter substance comparable to native bone tissue. Bone formation and transmitter substance determination will be used to determine if an optimized model has been reached compared to cell well plates and the original P3D Scaffold. The models and comparators are then to be introduced to co-cultures of hMSCs and cancer cell lines to construct tumoroid models that will be subjected to chemotherapeutic treatment. The effects of the chemotherapeutic responses are measured and compared across sample groups. The results analyzed from the tumoroid models will be compared to literature.

Rie Andersen Lassen

Research Intern, Biomedicine

 

Background to the study

Bone metastasis, which is a transfer of cancer from solid tumors to bone, commonly originates from thyroid, gynecologic, breast, colorectal, lung, prostate, and melanoma [1]. The two most frequent cancer types that metastases to bone originate from is breast and prostate cancer. Unfortunately, there is currently no effective treatment once the tumor cells have metastasized to bone. Finding treatments of metastases to bone is therefore a major challenge in the field of research [1, 2]. One of the problems in this research is the design of a proper bone marrow model [3], especially because bone marrow has a very complex 3D microenvironment [2].

 

Models used for research on metastasis to bone

To date, the models used for research on metastasis to bone have typically exploited animal models or 2D cell cultures using human cell lines. However, animal models differ in physiology and metabolism between species and 2D cell cultures of human cell lines cannot imitate the 3D microenvironment of metastases in bone [3, 4]. Meanwhile, organoids enable cell-to-cell contact by providing a 3D environment [3]. Organoids may overcome some of the challenges that 2D cell cultures and animal models (such as Caenorhabditis eleangans, Drosophila melanogaster and Mus musculus) faces. Still, this depends on the construct of the human organoid.

 

Introducing organoids in research

For most human organoids, the advantages are that they are; human-derived (representing the human physiology in contrast to 2D cell cultures using human cell lines); and relatively easy to genetically manipulate in combination with induced pluripotent stem cells. Finally, organoids are less costly than mouse models but are relatively costly compared to yeast, fly models, and traditional cell lines [5].

To some extent, the aim of human organoids usage is to limit the usage of animals for testing – by utilizing the physiological features of the technology. However, unfortunately, human organoids cannot entirely exclude the use of animal models as animals include molecular pathways and metabolism that organoids are unable to promote  [3, 5]. Overall, organoids open the opportunity for more complex studies than 2D cell cultures while limiting the usage of animals in research of the pathophysiology of disease and the development of drugs and personalized medicine [5].

An organoid model that is under development is the the combination of hMSCs and the P3D Scaffold by Particle3D, which mimics the mineralized bone environment and can be used to grow tumoroids for research on metastases to bone [6].

 

References

  1. Fornetti, J., A.L. Welm, and S.A. Stewart, Understanding the Bone in Cancer Metastasis. J Bone Miner Res, 2018. 33(12): p. 2099-2113.
  2. Maurizi, A. and N. Rucci, The Osteoclast in Bone Metastasis: Player and Target. Cancers (Basel), 2018. 10(7).
  3. Scheinpflug, J., et al., Journey into Bone Models: A Review. Genes (Basel), 2018. 9(5).
  4. Fontoura, J.C., et al., Comparison of 2D and 3D cell culture models for cell growth, gene expression and drug resistance. Mater Sci Eng C Mater Biol Appl, 2020. 107: p. 110264.
  5. Kim, J., B.K. Koo, and J.A. Knoblich, Human organoids: model systems for human biology and medicine. Nat Rev Mol Cell Biol, 2020. 21(10): p. 571-584.
  6. Wellejus, M. Miniature tumors can be grown on P3D scaffolds for cancer research. 2020 Oct 21, 2020.