Chondrogenic Potential of Adipose Stem Cells and Chondrons In Vitro and Their Regenerative Capacity In Vivo

Background and Aim: In articular cartilage regeneration, adipose tissuestem cells (ASCs) and chondrocytes have been used in several studies.Chondrocyte with peri-cellular matrix (PCM) is called chondronpreserves its chondrocyte phenotype. Also, there are promising data frompreclinical studies indicate the importance of using mesenchymal stemcells for clinical purposes. This study investigated chondrogenic potentialand regenerative effects of ASC and chondron in vitro and in vivo.Methods: In vitro study on human ASCs, chondrons and combinationof them cultured for 4 days. The gene expressions of Sox9, runtrelatedtranscription factor-2 (Runx2), aggrecan (AGG), cartilageoligomeric matrix protein (COMP), collagen type 10 (Col10), matrixmetalloproteinase-13 (MMP13) were assessed for different stages ofchondrogenesis at day 4 by real-time RT-PCR. In vivo study ASC, from theperi-renal fat of male rat and chondron from primary newborn rat hyalinecartilage were isolated. ASCs were cultured for at least three passages invitro. Six weeks after OA induction, rats were randomly distributed in fivegroups of control, osteoarthritic, ASC, chondron and co-cultured. ASCs(107), chondrons (107) and the combination of chondrons and ASCs(107) were injected into intra-articular space of the rat knee. The effect oftreatments was evaluated by microscopic examinations.Results: PAS staining showed PCM of chondrons. The gene expression ofSox9, Agg, COMP and link protein results of chondrons were significantlyhigher than ASCs and coASCs at day 4. Histologic finding of in vivo studyshowed that more repair of the articular surface in ASC and coculturegroups versus chondron group. H&E staining technique showed evidenceof repair site of articular surface without erosion and fibrillation versusOA group which showed a thin layer of hyaline cartilage over tidemarkand spontaneous fibrocartilage formation.Conclusion: ASCs improve articular hyaline cartilage formation thanchondron instead of high chondrogenic potential of chondrons in vitro.Joint microenvironment may be an effective factor on regenerationpotency of different cell types.

کلیدواژه ها:

Adipose stem cell ، Cell therapy ، Chondron ، Co-culture ، Induced osteoarthritis