Tag Archives: Holly Evans

Cartilage; the ‘official tissue’ of tissue engineering

What is this fascination with cartilage? For the second time this week (see yesterday’s [April 30, 2014] posting: Replacement cartilage grown on laboratory chip)  there’s a news item about a team, this time from Columbia University School of Engineering and Applied Sciences (aka Columbia Engineering), growing cartilage. From an April 30, 2014 news item on ScienceDaily,

Researchers at Columbia Engineering announced today that they have successfully grown fully functional human cartilage in vitro from human stem cells derived from bone marrow tissue. Their study, which demonstrates new ways to better mimic the enormous complexity of tissue development, regeneration, and disease, is published in the April 28 Early Online edition of Proceedings of the National Academy of Sciences (PNAS).

“We’ve been able — for the first time — to generate fully functional human cartilage from mesenchymal stem cells by mimicking in vitro the developmental process of mesenchymal condensation,” says Gordana Vunjak-Novakovic, who led the study and is the Mikati Foundation Professor of Biomedical Engineering at Columbia Engineering and professor of medical sciences. “This could have clinical impact, as this cartilage can be used to repair a cartilage defect, or in combination with bone in a composite graft grown in lab for more complex tissue reconstruction.”

An April 30, 2014 Columbia Engineering news release by Holly Evans, which originated the news item, provides some insight into the issues associated with tissue engineering and cartilage,

For more than 20 years, researchers have unofficially called cartilage the “official tissue of tissue engineering,” Vunjak-Novakovic observes. [emphasis mine] Many groups studied cartilage as an apparently simple tissue: one single cell type, no blood vessels or nerves, a tissue built for bearing loads while protecting bone ends in the joints. While there has been great success in engineering pieces of cartilage using young animal cells, no one has, until now, been able to reproduce these results using adult human stem cells from bone marrow or fat, the most practical stem cell source. Vunjak-Novakovic’s team succeeded in growing cartilage with physiologic architecture and strength by radically changing the tissue-engineering approach.

The general approach to cartilage tissue engineering has been to place cells into a hydrogel and culture them in the presence of nutrients and growth factors and sometimes also mechanical loading. But using this technique with adult human stem cells has invariably produced mechanically weak cartilage. So Vunjak-Novakovic and her team, who have had a longstanding interest in skeletal tissue engineering, wondered if a method resembling the normal development of the skeleton could lead to a higher quality of cartilage.

(I love the combination of “unofficially” with “official.”) Getting back to the cartilage research, the news release goes on to describe a new technique for engineering cartilage,

Sarindr Bhumiratana, postdoctoral fellow in Vunjak-Novakovic’s Laboratory for Stem Cells and Tissue Engineering, came up with a new approach: inducing the mesenchymal stem cells to undergo a condensation stage as they do in the body before starting to make cartilage. He discovered that this simple but major departure from how things were usually being done resulted in a quality of human cartilage not seen before.

Gerard Ateshian, Andrew Walz Professor of Mechanical Engineering, professor of biomedical engineering, and chair of the Department of Mechanical Engineering, and his PhD student, Sevan Oungoulian, helped perform measurements showing that the lubricative property and compressive strength—the two important functional properties—of the tissue-engineered cartilage approached those of native cartilage. The researchers then used their method to regenerate large pieces of anatomically shaped and mechanically strong cartilage over the bone, and to repair defects in cartilage.

“Our whole approach to tissue engineering is biomimetic in nature, which means that our engineering designs are defined by biological principles,” Vunjak-Novakovic notes. “This approach has been effective in improving the quality of many engineered tissues—from bone to heart. Still, we were really surprised to see that our cartilage, grown by mimicking some aspects of biological development, was as strong as ‘normal’ human cartilage.”

The team plans next to test whether the engineered cartilage tissue maintains its structure and long-term function when implanted into a defect.

Here’s a link to and a citation for the research paper,

Large, stratified, and mechanically functional human cartilage grown in vitro by mesenchymal condensation by Sarindr Bhumiratana, Ryan E. Eton, Sevan R. Oungoulian, Leo Q. Wan, Gerard A. Ateshian, and Gordana Vunjak-Novakovic. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1324050111

This paper is behind a paywall.

I have an observation about both this and the other cartilage story (Replacement cartilage grown on laboratory chip) featured here. It looks to me as if these two areas of research could be complementary. The ‘laboratory chip’ story is about a new way to use 3D printing to produce cartilage more quickly where this Columbia Engineering story is about better mimicking processes in the body to engineer stronger, more resilient cartilage. Taken separately or together cartilage tissue engineering has had an exciting week.