A comparative assessment of cartilage and joint fat pad as a potential source of cells for autologous therapy development in knee osteoarthritis

Objectives. The utility of autologous chondrocytes for cartilagerepair strategies in older subjects with osteoarthritis (OA)may be limited by both age-related and disease-associated declinein chondrogenesis. The aim of this work was to assess OA Hoffa'sfat pad as an alternative source of autologous chondroprogenitorcells and to compare it with OA chondrocytes derived from differentareas of cartilage. Methods. Cartilage and fat pad tissue digests were obtainedfrom 26 subjects with knee OA and compared with normal bonemarrow (BM) mesenchymal stem cells (MSCs) with respect to theirin vitro colony-forming potential, growth kinetics, multipotentialityand clonogenicity. Flow cytometry was used to investigate theirMSC marker phenotype. Results. Expanded cultures derived from eroded areas of cartilagewere slightly more chondrogenic than those derived from macroscopicallynormal cartilage or chondro-osteophytes; however, all cartilage-derivedcultures failed to maintain their chondrogenic potency followingextended expansion. In contrast, OA fat pads contained highlyclonogenic and multipotential cells with stable chondrogenicpotency in vitro, even after 16 population doublings. Standardcolony-forming assays failed to reflect the observed functionaldifferences between the studied tissues whereas flow cytometryrevealed higher levels of a putative MSC marker low-affinitygrowth factor receptor (LNGFR) on culture expanded fat pad-derived,but not cartilage-derived, MSCs. Conclusions. In contrast to OA cartilage from three differentsites, OA Hoffa's fat pad contains clonogenic cells that meetthe criteria for MSCs and produce multipotential cultures thatmaintain their chondrogenesis long term. These findings havebroad implications for future strategies aimed at cartilagerepair in OA. KEY WORDS: Mesenchymal Stem Cells, Osteoarthritis, CartilageSubmitted 7 February 2007; revised version accepted 17 July 2007.