New Study Uses Endogenous Recruitment of Stem Cells to Make New Joint
A new article in the The Lancet suggest that the entire articular surface of a hip joint may be able to regenerate without cell transplantation using the body’s own stem cells.
Professor Jeremy Mao of Columbia University Medical Center, New York and colleagues tested the hypothesis that the articular surface of the synovial joint can regenerate with a biological cue to recruit endogenous stem cells rather than using the more common approach of direct transplantation of the stem cells.
The researchers conducted a proof of concept study in which the surface morphology of a rabbit proximal humeral joint was captured with laser scanning and reconstructed by computer-aided design to fabricated an anatomically correct bioscaffold composed of poly-ɛ-caprolactone and hydroxyapatite.
This bioscaffold was then used to replace the entire articular surface of the forelimb joint of mature rabbits which had been surgically excised. The replacement bioscaffolds were spatially infused with transforming growth factor β3 (TGFβ3)-adsorbed or TGFβ3-free collagen hydrogel.
Ten rabbits received TGFβ3-infused bioscaffolds, ten received TGFβ3-free bioscaffolds, and three rabbits underwent humeral-head excision without bioscaffold replacement.
The rabbits were assessed for locomotion and weight bearing at 1—2, 3—4, and 5—8 weeks after surgery. At 4 months, the regenerated cartilage samples were removed from the rabbits and assessed for surface fissure, thickness, density, chondrocyte numbers, collagen type II and aggrecan, and mechanical properties.
The researchers found all 10 rabbits in the TGFβ3-delivery group resumed weight bearing and locomotion by 3—4 weeks after surgery, more consistently than those in the TGFβ3-free group. Defect-only rabbits limped at all times.
At 4 months after surgery, TGFβ3-infused bioscaffolds were fully covered with hyaline cartilage in the articular surface whereas TGFβ3-free bioscaffolds had only isolated cartilage formation. No cartilage formation occurred in defect-only rabbits.
The new cartilage formed in the TGFβ3 delivery group had compressive and shear properties consistent with native articular cartilage. TGFβ3 delivery recruited roughly 130% more cells in the regenerated articular cartilage than did spontaneous cell migration without TGFβ3.
"This is the first time an entire joint surface was regenerated with return of functions including weight bearing and locomotion," said Professor Jeremy Mao of Columbia University Medical Center, New York.
At this time, there are no trials in human patients.
Regeneration of the Articular Surface of the Rabbit Synovial Joint by Cell Homing: a Proof of Concept Study; Chang H Lee PhD, James L Cook DVM, Avital Mendelson MS, Eduardo K Moioli PhD, Hai Yao PhD, Prof Jeremy J Mao PhD; The Lancet, Early Online Publication, 29 July 2010; doi:10.1016/S0140-6736(10)60668-X