Fight Aging!

Far too little work in the medical research and development communities is focused on prevention or early intervention. It should always be easier to fix the early stages of a developing problem, medical or otherwise, and age-related diseases are no exception. Yet much of the development of therapies is focused on late stage disease rather than earlier, or even preclinical stages of the path to suffering and dysfunction. We might blame some of this on regulation that insists on treating only clearly defined disease, or on the tendency of researchers to study the end results of disease rather than the initial path to disease.

Regardless, the work described in today's research materials is an example of the sort of research and development that I'd like to see more of. The scientists involved aim to intervene in osteoarthritis by repairing damaged cartilage, but at earlier stages in the condition than is normally attempted, a point at which repair is an easier prospect for today's capabilities in cartilage tissue engineering. The less tissue that must be replaced, the more likely a tissue engineering strategy is to work.

Stopping arthritis before it starts

Osteoarthritis occurs when the protective cartilage that coats the ends of the bones breaks down over time, resulting in bone-on-bone friction. The disorder, which is often painful, can affect any joint, but most commonly affects those in our knees, hips, hands, and spine. To prevent the development of arthritis and alleviate the need for invasive joint replacement surgeries, the researchers are intervening earlier in the disease. "In some patients joint degeneration starts with posttraumatic focal lesions, which are lesions in the articular (joint) cartilage ranging from 1 to 8 cm2 in diameter. Since these can be detected by imaging techniques such as MRI, this opens up the possibility of early intervention therapies that limit the progression of these lesions so we can avoid the need for total joint replacement."

That joint preservation technology is a therapeutic bio-implant, called Plurocart, composed of a scaffold membrane seeded with stem cell-derived chondrocytes - the cells responsible for producing and maintaining healthy articular cartilage tissue. Building on previous research to develop and characterize the implant, the current study involved implantation of the Plurocart membrane into a pig model of osteoarthritis. This is the first time an orthopaedic implant composed of a living cell type was able to fully integrate in the damaged articular cartilage tissue and survive in vivo for up to six months. Molecular characterization studies showed the bio-implant mimicked natural articular cartilage, with more than 95 percent of implanted cells being identified as articular chondrocytes. The cartilage tissue generated was also biomechanically functional - both strong enough to withstand compression and elastic enough to accommodate movement without breaking.

Long-term repair of porcine articular cartilage using cryopreservable, clinically compatible human embryonic stem cell-derived chondrocytes

Generation of articular chondrocytes from pluripotent stem cells (PSCs) has been challenging as most chondrogenic cells during development are fated to undergo hypertrophy and endochondral ossification rather than adopt an articular chondrocyte identity. We and others have generated articular-like chondrocytes from human pluripotent stem cells; we have subsequently shown that stable articular chondrocytes produced from GFP-labelled PSCs can engraft, integrate into and repair osteochondral defects in small animal models. Moreover, these human cells produce all layers of hyaline cartilage after 4 weeks in vivo, including a PRG4+ superficial zone. However, production scaling and assessment of long-term, clinically relevant functionality has so far limited the development of these protocols.

The Yucatan minipig presents an excellent model for pre-clinical assessment of potential orthopedic therapies due to structural similarities, comparable thickness of articular cartilage, and the ability to create defects of substantial volume; in addition, their size allows for cost-efficient care and observation for extended periods of time. Here we present data demonstrating long-term functional repair of porcine full-thickness articular cartilage defects with hyaline-like cartilage by scalable production of clinical grade human embryonic stem cell-derived immature articular chondrocytes.