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I'm from a maths background and I'm doing some research on mathematical models of cancer. I've come across a lot of literature mentioning "multicell spheroids" in the context of avascular tumours. I know that avascular means a lack of blood vessels, but I am having trouble finding an explanation for multicell spheroids. Are these some kind of model/approximation of a certain types of tumours, or are they actually a real phenomenon in and of themselves?

It would be great if someone could fill me in on what multicell spheroids actually are!

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They are three-dimensional cell cultures according to H Ma et al. 2012.

Multicellular tumor spheroids are one of the classic 3D culture models that can be applied to the development of anticancer drugs and treatments. By mimicking the 3D network of the cellular–matrix and cell–cell interactions, tumor spheroids resemble many aspects of the pathophysiologic environment within human tumor tissue.

Classical cell cultures are usually monolayer. Many of the differences between these cultures and real-life tissues has been overcome by 3D cultures according to Carver et al. 2014.

The multicellular tumor spheroid (MCTS), a three-dimensional model that closely resembles small avascular tumors and micrometastases, has been utilized as an intermediate between monolayer culture and in vivo studies for the screening of small-molecule drugs.

So is it a 'real life' entity or is it something that is computer generated? It is real life. Let's think of an organ. It's made up of a specific tissue(s) and a stroma that contains vascular, nervous and other components that supply nutrients and limit the organ's specific tissue. This structure develops in vivo in 3D. The blood vessels will follow tissue development in a tree-like 3D structure in order to reach to all cells. But what do you do with lab cell cultures? There are no blood vessels there. How do you supply nutrients to all cells? That is why most in vitro cell cultures are developed in monolayer structure. Yet cells are 3D structures. They are joined together in a tissue by intercellular junctions. Monolayer limits this joining to a single plane. Moreover, when it comes to cancer cells which have specific properties (they lose junctions and start to move) the monolayer model becomes limited. This is how spheroids have become a better model for studying in vivo processes using in vitro cell cultures.

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  • $\begingroup$ So is it a 'real life' entity or is it something that is computer generated? Sorry if the question is dumb but I have no experience in biology so that is all complete jargon to me unfortunately. If you could explain like I'm 5 that would be great! $\endgroup$
    – sonicboom
    May 26, 2015 at 16:51
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Classical cell culture is a monolayer of cells on the surface of a cell culture dish. These cultures differ strongly from the microenvironment which cells have in tumors, as the cells only interact with their direct neighbours, but have otherwise a relatively optimal supply of nutrients and oxygen.

In a real-life tumor, a cell mass is growing uncontrolledly in all three dimensions of the space, producing these typical "knots" of tumors. As long as these are not getting supplied by own blood vessels (meaning they are vascularized) supply of oxygen, nutrients and growth factors and hormones differ very much between the cells in the outer layers of the tumor and cells in the inside. This causes different levels of stress and also physiological reactions of the cells. This looks like in the figure below (from here):

enter image description here

To resemble these micro-environments for research (and 2D and 3D cell culture differ quite a bit in the results), people are trying to simulate these. Technically this is achieved by embedding small amounts of cells (typically a few hundred) into a gel matrix (for example matrigel or collagen) which is getting hard, and let the cells grow in small drops. If the conditions are right, the cells will develop into these multicellular spheroids.

You can even mix different cell types (for example tumor cells and cells which are usually present in the tissue where the tumor grows) to get an even better simulation. See the references for some more details.

References:

  1. Three-dimensional cell cultures: from molecular mechanisms to clinical applications.
  2. Recent advances in three-dimensional multicellular spheroid culture for biomedical research.
  3. Spherical cancer models in tumor biology.
  4. Development of 3D in vitro technology for medical applications.
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  • $\begingroup$ Very nice answer, cheers! $\endgroup$
    – sonicboom
    May 26, 2015 at 17:21

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