Cartilage formed with stem cells

Cartilage injuries are difficult to treat. Current methods are mainly based on transplantation of healthy cartilage portion into the damaged area. Such a procedure affects healthy cartilage. Moreover, the cartilage gradually degrades with age.

Researchers from the University of Pennsylvania, USA,
have developed the innovative approach of growing new cartilage from a patient’s own stem cells.

The study was conducted by Jason Burdick, Associate Professor of Bioengineering School of Engineering and Applied Sciences (Department of Bioengineering in the School of Engineering and Applied Science) and Mauke Robert, Associate Professor of the Department of Orthopaedic Surgery School of Medicine Perelman (Department of Orthopaedic Surgery in Penn’s Perelman School of Medicine.

The study is published in «Proceedings of the National Academy of Sciences», the Journal of the National Academy of Sciences of the USA.

“We started our research with focal lesions – such as sports injuries,” – Jason Burdick said. “Our further research is aimed to replace the surface of the cartilage destroyed with age. At the moment, we are trying to find the most suitable conditions for growing cartilage from adult human mesenchymal stem cells. “
“In the process of aging cartilage cell viability decreases, so the cartilage repair is ineffective if using adult chondrocytes,” – Robert Mauke says.

“Mesenchymal stem cells, characterized by potent proliferative potential are perfect for this.”
Burdick and his colleagues studied the mesenchymal stem cells that can “transform” into the cells of bone, cartilage and adipose tissue for a long time. His team was particularly interested in the conditions that allow stem cells to differentiate into chondrocytes.

One of the problems faced by researchers is that, despite the low density of adult chondrocytes in tissue, the actual formation of cartilage begins at a direct interaction of cells located close to each other.

“In the hydrogels used for the cultivation of tissue engineered cartilage cells located at a distance from each other, which leads to loss of interaction signals. That’s when we started thinking about the cadherins, molecules by which cells interact with each other, particularly in the early stages of differentiation into chondrocytes, “- Jason Burdick says.

Researchers added peptide sequence mimicking cadherin connection for simulation of conditions for the growth of cells into the hydrogel.

“At the present time a direct link between cadherins and chondrogenesis is not well understood,” – Robert Mauke says: “We only know that simulating cellular interactions in the early stages of tissue generation leads to more cartilage formation. Blocking of interactions slows down the formation of cartilage.

This gel makes the cell ‘assume’ that it is surrounded by other cells.”To test the effectiveness of the gel with peptides that mimic cadherin, the researchers placed mesenchymal stem cells into different types of gels such as conventional hydrogel, hydrogel with disrupted, non-functional variants of the peptide, a peptide hydrogel, cadherin activity of which was blocked by antibodies.

The maximum amount of genetic markers of chondrogenesis among all cultured samples was identified in the mesenchymal stem cells cultured for a week in a gel containing cadherin-like peptides. In another experiment, cells were grown in a tested gel for four weeks. This is sufficient time for the beginning of formation of the cartilage matrix tested for different stresses such as mechanical stress.

Scientists concluded that the cartilage derived from a gel containing peptides is closest to a”natural” than the one grown in other control hydrogels.

The researchers also performed various tests by staining the gel slices for detecting the chondroitin sulphate and type-II collage which are part of the cartilage matrix. As it was shown before, gels peptide with contained the biggest amount of markers of tissue formation comparing to other hydrogels.

“In the near future it is important to study the behavior of obtained cells for prolonged stay under in vivo conditions”, – Robert Mauke says.