Microenvironment and phenotypic stability specify tissue formation by human articular cartilage-derived cells in vivo

Francesco Dell'Accio, Cosimo De Bari, Frank P Luyten

Research output: Contribution to journalArticlepeer-review

116 Citations (Scopus)


During in vitro expansion, adult human articular cartilage-derived cells (HACDC) lose their phenotypic stability and capacity to form cartilage in vivo after 4-6 population doublings (PD). Nevertheless, HACDC can be efficiently expanded for up to 20 PD. Here we show that HACDC can generate cartilage, fibrous tissue, skeletal muscle, bone, and adipocytes depending on the balance between phenotypic stability and environmental cues. When 5 x 10(6) cells were injected intramuscularly into nude mice, early-passage (EP)-HACDC formed cartilage; late-passage (LP)-HACDC formed mostly fibrous tissue, but a limited number of cells contributed to muscle formation. When 0.5 x 10(6) cells were injected into regenerating mouse muscle, both EP- and LP-HACDC integrated with host myofibers and expressed muscle genes, but a number of EP-HACDC maintained collagen type II expression. HACDC seeded into Collagraft and implanted subcutaneously into nude mice formed scattered bone islands displaying immunoreactivity for human osteocalcin, and expressing human bone-specific genes. Importantly, neither collagen type II transcript nor cartilage tissue was detected at 8 weeks after implantation. Myogenic, osteogenic, and adipogenic differentiation was induced in vitro using specific culture conditions. These findings provide evidence that in vivo tissue formation by HACDC is specified by a balance between environmental cues and the inherent phenotypic stability.
Original languageEnglish
Pages (from-to)16-27
Number of pages12
JournalExperimental Cell Research
Issue number1
Publication statusPublished - 1 Jul 2003


  • Adipocytes
  • Animals
  • Bone and Bones
  • Cartilage, Articular
  • Cell Communication
  • Cell Differentiation
  • Cell Survival
  • Cells, Cultured
  • Collagen Type II
  • Connective Tissue
  • Cues
  • Humans
  • Mice
  • Mice, Nude
  • Muscle, Skeletal
  • Osteocalcin
  • Phenotype
  • Stem Cell Transplantation
  • Stem Cells


Dive into the research topics of 'Microenvironment and phenotypic stability specify tissue formation by human articular cartilage-derived cells in vivo'. Together they form a unique fingerprint.

Cite this