Lifelike bone grown from single cells

The cultured bone is particularly suitable for testing and designing new treatments for bone disorders

Researchers from Radboudumc Nijmegen and Eindhoven University of Technology have intertwined various bone cells into an ‘organoid’, a mini-organ that can independently make new, hard bone tissue. With this most complete 3D model of bone formation to date, the biochemical processes can be studied in unprecedented detail and thus answer the many open questions about bone formation. In addition, the cultured bone is particularly suitable for testing and designing new treatments for bone disorders such as osteoporosis or osteogenesis imperfecta.

Imagine that a piece of bone tissue is grown in the lab with stem cells from your bone marrow. And then doctors look at which drugs have the desired effect on your bones. In this way, a treatment plan would be tailor-made for everyone, whereby it is already clear in advance what the best approach can be.

That vision of the future is no longer science fiction now that researchers from Eindhoven University of Technology and Radboudumc have actually realized the first part: growing a lifelike piece of bone tissue from human stem cells. This is the first ‘organoid’ made of bone, a simplified version of the original, they report Tuesday, March 9 in the journal Advanced Functional Materials.

Cohesive picture
“This is the first time we present the complete picture of bone formation,” says Sandra Hofmann, Bioengineering Bone researcher at TU / e. And that is very important: exactly how our bones are formed is still largely a mystery. Bone is a very complex material where on the one hand countless cells and processes interact with each other, and on the other hand an ingenious scaffold (matrix) of collagen is built up that provides the firmness. Much is now known about individual parts, but a coherent picture has been lacking until now.

Three types of cells play a major role in bone formation: osteoblasts (which build bone tissue), osteoclasts (which break down bone) and osteocytes (which regulate the build-up and breakdown of bone). “Most of the studies to date have focused on one of these types of cells, but that’s not a good representation of real tissue,” says Hofmann. “We present here a piece of grown bone that contains two of these types of cells: osteoblasts and osteocytes. We now see that we can only make lifelike bone with these two cell types. ”

Getting wiser from molecular poking
And perhaps more importantly: the system also behaves exactly like bone at an early stage, according to Anat Akiva, Cell Biology researcher at Radboud university medical center. “We show that both types of cells produce the proteins they need for their functionality, showing in great detail that the hard bone material that we see in our own bones is formed.”

The fact that there is now a simplified representation of the formation of bone at the molecular level offers unprecedented possibilities, according to the researchers. “A bone consists of 99% collagen and minerals, and the rest is protein,” explains Professor Nico Sommerdijk of Radboudumc. “What is the role of those proteins? How do they support bone formation? Never before have we been able to view the milestones of this process at a molecular level. ”

And with that, they immediately have a good entrance for researching painful bone problems such as ‘brittle bone disease’ and the possible treatments. “Remember, the origins of many conditions are at the molecular level – and so is the treatment,” Akiva says. “In fact, we now have a simple system in a reliable environment in which we can poke and watch how the bone cells respond to the stimuli we give.”

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