Cartilage Repair Without Scaffolds

Researchers are working on a method of delivering cells for cartilage regrowth in aged joints that doesn't use a porous scaffold in order to guide cell growth, but rather relies on the engineering of specific cell characteristics. In theory this should produce a better end result:

In many cases, the cause of age-related joint pain is a loss of hyaline cartilage, which does not have the capacity to regenerate, meaning once gone it is gone forever. Hyaline cartilage is constituted of chondrocytes and its secretions, extracellular matrix (ECM) proteins, which includes collagens II and XI. They do not include collagen I, which is the primary collagen in fibrocartilage, or scar tissue. The key to a successful recovery then is to introduce into the deteriorated cartilage chondrocytes that secrete only hyaline cartilage ECM proteins.

One of the most common strategies for treating hyaline cartilage damage is autologous chondrocyte transplantation. This technique involves acquiring hyaline cartilage from a biopsy and then transplanting it to the injured site. Because the biopsy is smaller than the area that needs repair, the chondrocytes must be expanded, a task that requires enzymatic digestion of the ECM proteins. Unfortunately, the expansion causes the chondrocytes to secrete collagen I, which is why the presence of fibrous tissue is inevitable after such operations.

To solve this problem, researchers report a new protocol that expands not chondrocytes, but induced pluripotent stem (iPS) cells. When a sufficient number of iPS cells are expanded, the protocol then calls for the researchers to differentiate the cells into chondrocytes. Because these chondrocytes are differentiated directly from iPS cells, there is no need to digest ECM proteins, which avoids the problem of fibrous tissue and allows for only hyaline cartilage to be synthesized. Another advantage to this method is that it avoids the use of artificial scaffolds. In other studies artificial scaffolds are included into the transplant to provide support until the chondrocytes begin secreting their own ECM proteins. However, it is unclear if artificial materials prevent optimal integration into the cartilage. Because the chondrocytes have already begun secreting ECM proteins, they can be transplanted without scaffolds.

The team transplanted their particles into three animal models: mouse, rat and mini-pig, finding positive signs for integration and maintenance. "These findings are only preliminary, but they show good indications of safety. The next step is to find the best conditions for transplantation in larger animals before we can consider patient treatment."



Two questions for anyone so knowledgeable:

1. When might this technology be available for use in humans?
2. How would the significantly aged environment affect transplanted chondrocytes and their growth/function in comparison to chondrocytes in the young body?

Posted by: Seth at February 27th, 2015 11:15 AM

@Seth: For research at this stage, a decade is always a fair guess. Say five years to get to human trials and another five years to wade through that, assuming it all pans out and doesn't fall off the radar due to other approaches drawing off attention and funding.

The aged environment is clearly not good for all sorts of cells, but the situation differs by tissues. I'd have to go digging to see if anyone has worked on that topic for cartilage. Nothing detailed turned up on a shallow, quick search. See the sparse comments in the conclusion of this review for example:

Posted by: Reason at February 27th, 2015 6:30 PM

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