McGowan Institute for Regenerative Medicine associate director Rocky Tuan, PhD, is the director of the Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, and the executive vice chairman for orthopaedic research at the University of Pittsburgh. Dr. Tuan's research focuses on the development, growth, function, and health of the musculoskeletal system, the biology of adult stem cells, and the utilization of this knowledge to develop technologies that will regenerate and/or restore function to diseased and damaged musculoskeletal tissues. In a feature story in Science News, author Nathan Seppa provides an overview of the research efforts on cartilage creation, including the contributions made by the team of researchers in Dr. Tuan's lab.
Osteoarthritis (OA) is the most common joint disorder, which is due to aging and wear and tear on a joint. Cartilage is the firm, rubbery tissue that cushions your bones at the joints, and allows bones to glide over one another. If the cartilage breaks down and wears away, the bones rub together. This causes pain, swelling, and stiffness. Bony spurs or extra bone may form around the joint. The ligaments and muscles around the joint become weaker and stiffer.
Mr. Seppa explains that some orthopedists consider cartilage regeneration the holy grail of their field. Confronted with many people living longer lives, orthopedists have used surgery to clean out damaged joints, braces to stabilize a wobbly gait, and artificial knees and hips to replace damaged bone ends, a last resort against osteoarthritis. All these treatments are short of growing new cartilage.
But now, Mr. Seppa learned that with the help of stem cells, a new generation of bioengineers is coming close to cracking the code for cartilage regrowth. Stem cells have yet to choose a career path, a characteristic that makes them attractive future cartilage-creators. The very simple version of the stem cell approach is: Stem cells are extracted from a patient, geared up to become chondrocytes, wrapped in a favorable mix of compounds, and then inserted into damaged joints. The cells take it from there and create replacement cartilage.
The recipe for the compound mixture to encourage growth and cartilage formation is still a mystery, but scientists have identified several possible ingredients. Growth factors are one. Those studied include TGF-beta, FGF-2, kartogenin, and a protein called vimentin. To differentiate into a chondrocyte, a stem cell must take on a round shape, says Dr. Tuan. He and his colleagues found that vimentin nudges bone marrow stem cells toward becoming rounded like chondrocytes. Extra vimentin also boosts genes instrumental in making type 2 collagen, Dr. Tuan's team reported in 2010 in the Journal of Cellular Biochemistry.
Scaffolding material gives cartilage compound mixtures a base to form potential cartilage patches. About a decade ago, Dr. Tuan and one of his former PhD students, Wan-Ju Li, PhD, now a tissue engineer at the University of Wisconsin-Madison, became interested in building a synthetic scaffold resembling the naturally occurring one, onto which they could seed stem cells. While still at the National Institutes of Health, they used a process called electrospinning to cast nanofibers of polymer into a structure resembling cartilaginous matrix. Those first webs have since been improved and made into a biodegradable cartilage scaffold.
Mr. Seppa reports that in 2009, Drs. Tuan and Li tested their scaffold, seeding it with human stem cells to create a patch that was then inserted into pigs with cartilage damage in their knees. Some pigs received scaffolding seeded with mature chondrocytes. The researchers allowed the pigs, with some restrictions, to put weight on the knees almost immediately, since routine compression is the norm for cartilage. After 6 months, the stem cells had grown into chondrocytes that made hyaline cartilage that outperformed the fibrocartilage made by the mature chondrocytes.
Researchers agree more work is needed to bring stem cell–based cartilage regeneration to the clinic. Dr. Li suspects the technical problems might be solved in the next 5 years or so, with another 5 years needed to sort out regulatory and insurance issues.
Today, Dr. Li has students who are surgeons, still busy learning how to replace knees and hips. "I was joking with them," he says, "saying, 'You guys are going to have to find a new job soon.'"
Abstract (The intermediate filament vimentin regulates chondrogenesis of adult human bone marrow-derived multipotent progenitor cells. Brent E. Bobick, Rocky S. Tuan, Faye H. Chen. Journal of Cellular Biochemistry; Volume 109, Issue 1, pages 265–276, 1 January 2010.)