Mesenchymal stromal cell chondrogenesis under ALK1/2/3-specific BMP inhibition: a revision of the prohypertrophic signalling network concept.
Solvig DiederichsSimon I DreherSarah Anna NüeschSven SchmidtChristian MerleWiltrud RichterPublished in: Stem cell research & therapy (2024)
Overall, our data show that BMP-ALK1/2/3 inhibition cannot program mesenchymal stromal cells toward stable chondrogenesis. BMP-ALK1/2/3 signalling is no driver of hypertrophic MSC misdifferentiation and BMP receptor induction is not an adverse prohypertrophic side effect of TGF-β that leads to endochondral MSC misdifferentiation. Instead, the prohypertrophic network comprises misregulated PTHrP/hedgehog signalling and WNT activity, and a potential contribution of TGF-β-ALK4/5-mediated SMAD1/5/9 signalling should be further investigated to decide about its postulated prohypertrophic activity. This will help to successfully engineer cartilage replacement tissues from MSCs in vitro and translate these into clinical cartilage regenerative therapies.
Keyphrases
- mesenchymal stem cells
- bone marrow
- advanced non small cell lung cancer
- transforming growth factor
- stem cells
- umbilical cord
- cell therapy
- bone regeneration
- epithelial mesenchymal transition
- gene expression
- total knee arthroplasty
- extracellular matrix
- single cell
- big data
- electronic health record
- artificial intelligence
- tyrosine kinase
- tissue engineering
- machine learning
- total hip arthroplasty
- high resolution