Autophagy is involved in mesenchymal stem cell death in coculture with chondrocytes

Carlo Alberto Paggi, Amel Dudakovic, Yao Fu, Catalina Galeano Garces, Mario Hevesi, Daniela Galeano Garces, Allan B. Dietz, Andre van Wijnen*, Marcel Karperien*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
69 Downloads (Pure)


Objective: Cartilage formation is stimulated in mixtures of chondrocytes and human adipose–derived mesenchymal stromal cells (MSCs) both in vitro and in vivo. During coculture, human MSCs perish. The goal of this study is to elucidate the mechanism by which adipose tissue–derived MSC cell death occurs in the presence of chondrocytes.

Methods: Human primary chondrocytes were cocultured with human MSCs derived from 3 donors. The cells were cultured in monoculture or coculture (20% chondrocytes and 80% MSCs) in pellets (200,000 cells/pellet) for 7 days in chondrocyte proliferation media in hypoxia (2% O2). RNA sequencing was performed to assess for differences in gene expression between monocultures or coculture. Immune fluorescence assays were performed to determine the presence of caspase-3, LC3B, and P62.

Results: RNA sequencing revealed significant upregulation of >90 genes in the 3 cocultures when compared with monocultures. STRING analysis showed interconnections between >50 of these genes. Remarkably, 75% of these genes play a role in cell death pathways such as apoptosis and autophagy. Immunofluorescence shows a clear upregulation of the autophagic machinery with no substantial activation of the apoptotic pathway.

Conclusion: In cocultures of human MSCs with primary chondrocytes, autophagy is involved in the disappearance of MSCs. We propose that this sacrificial cell death may contribute to the trophic effects of MSCs on cartilage formation.

Original languageEnglish
Pages (from-to)969S-979S
Issue number2_suppl
Publication statusPublished - 1 Dec 2021


  • UT-Hybrid-D
  • chondrocytes
  • coculture
  • mesenchymal stem cells
  • pellet
  • autophagy


Dive into the research topics of 'Autophagy is involved in mesenchymal stem cell death in coculture with chondrocytes'. Together they form a unique fingerprint.

Cite this