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Joint movement may help stem cells regenerate skeletal tissue
The endogenous cellular pool it creates could one day be tapped to treat musculoskeletal disorders.
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COURTESY OF DIDIER F. MOUKOKO |
French researchers recently determined that in the presence of joint motion, a periosteal flap with a cambium layer containing osteochondral precursor cells, transplanted to the knees of rabbits, may have stimulated mesenchymal stem cells at the recipient site.
This likely contributed to regenerative skeletal changes, the investigators said.
Such changes were seen in the medullary cavity, menisci and free joint space where production of cartilage, bone, and fibrous and muscular tissue was identified. The effect was sustained up to eight weeks.
The researchers theorized this occurred because the animals continued to move their knee joints. Where post-transplant joint movement was prohibited, cellular events evocative of embryological phases of joint cavity formation were seen initially but ceased in a few days in an earlier study by these investigators.
“The results confirmed a quantitative and qualitative biological influence by motion on the stimulation of blastemal cell proliferation and differentiation. At the same time, stimulation and multilineage differentiation of cellular elements not originating from the flap was noted in the adjacent joint cavity, muscles and bone marrow,” Didier F. Moukoko, MD, told Orthopedics Today.
Moukoko, at the Service Orthopédie Pédiatrique at CHU Lapeyronie in Montpellier, France, presented results at the 78th Annual Meeting of Sociéte Française de Chirurgie Orthopédique et Traumatologique (SOFCOT).
18 rabbits
The experiment involved 18 New Zealand rabbits. Researchers transferred a vascularized periosteal flap to the inner side of one knee of each animal. It was attached at the periphery with continuous sutures so the flap’s soft tissue would contact the distal femur, the tibia and periarticular tissues between the two areas. Postoperatively, the animals were permitted to walk and move normally.
Animals in a control group received a periosteal flap placed below the knee so it would not be subject to motion.
The animals were sacrificed between two days and eight weeks postop; histological sections were made of the regeneration and joint areas of the recipient knee. Researchers saw some key early-stage elements, the first of which was a suspected “proliferation of precursor cells apparently originating from the cambium layer of the periosteum, constituting a mass of immature cells, which later became differentiated,” Moukoko said.
Cells of unknown origin
The investigators also saw numerous cells of unknown origin that were free in the knee joint cavity and in various stages of mesenchymal tissue differentiation, including muscular lineage.
“We believe there are two possibilities: These are synovial stem cells or circulating stem cells,” he said. These “free cells” were first seen in the joint cavity between the second and fourth postop days and in the bone marrow cavity at the 10th postop day.
The same process was observed in the intermuscular septa in proximity to the vessels, Moukoko said. “In the vascular network in close contact with regeneration, monocyte-like cells suspected of being stem cells, due to their immunostaining characteristics, are observed in large numbers.”
These potential mechanisms for local or regional recruitment of stem cells for musculoskeletal healing suggest future cellular therapy and tissue engineering possibilities with clinical potential, he added.
For more information:
- Moukoko D, Pourquier D, Diméglio A. In vivo stimulations of mesenchymal stem cells in an animal model of skeletal tissue regeneration. #206. Presented at the 78th Annual Meeting of the Sociéte Française de Chirurgie Orthopédique et Traumatologique. Nov. 11-14, 2003. Paris.