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A NOVEL MODEL OF SPONTANEOUSLY DIFFERENTIATING CHONDROCYTES FOR REPLENISHMENT OF LOCAL ARTICULAR LESIONS



Abstract

Purpose: Hyaline cartilage lesion in a large weight bearing joint can lead, if not treated, to damage of the subchondral bone. Since cartilage tissue does not heal spontaneously, nor can it regenerate, joint functional restitution is based on temporary biological solutions. The only promising approach for recovering damaged joint and avoid its eventual deterioration is to restore the genuine surfacing of hyaline cartilage.

Methods: We have developed a novel primary chondrocytes culture based on a unique source of cartilage cells whereby a gradual collagenase separation yield a homogenous chondrocyte population, which unlike other cartilage source-derived cells preserve the capability of spontaneous differentiation into cartilage forming cells.

Results: Following a short period of intensive proliferation, the cells start to differentiate into polygonal shaped cells, expressing Cbfa1-the skeletal tissues specific transcription factor, type II collagen and cartilage proteoglycan; thus producing a genuine hyaline cartilage. The cultured chondrocytes also preserve their responsiveness toward local and systemic factors such as growth hormone, insulin, PTH and IGF1. Since, cartilage is an immuno-privileged tissue; non- autologous cartilage sources may also be successfully transplanted. We have shown that mourine and porcine-derived cells injected into rats afflicted (AIA) joints replenish the articular lesion with no signs of WBC infiltration. Since, prior to differentiation, these cells undergo an intensive proliferation phase they can also be transfected. We have also shown that osteoprotegerin (OPG)-firstly known for its activity as RANK ligand decoy receptor, has direct ameliorative effects on cartilage development. We have shown that OPG transfected chondrocytes preserve their typical morphological and functional features.

Conclusions: This model of primary chondrocyte culture, develop authentic resemblance to hyaline (surfacing) cartilage with similar physical and mechanical properties of the original tissue. These cells can be successfully transplanted into damaged joint of a foreign host. Hence, we propose that these primary spontaneously-differentiating chondrocytes, from non autologous source- can be suitable for replenishment of articular lesions as well as vehicle for local application of beneficial cytokines like OPG.

The abstracts were prepared by Orah Naor, IOA Co-ordinator and Secretary. Correspondence should be addressed to Israel Orthopaedic Association, PO Box 7845, Haifa 31074, Israel.