Mesenchymal stem cell signaling and differentiation

Our lab uses mesenchymal stem cells as a clinically relevant source for bone tissue engineering but also as a model system for differentiation and signal transduction. In the past we have used candidate small molecule approaches to control MSC osteogenic differentiation via protein kinase A signaling, but we also screened libraries for small molecules which mimic a hypoxia response. In both cases, small molecules affect the hMSC secretome. We recently even discovered surface topographies which induce thrombospondin-2 secretion.

Manipulation of the hMSC secretome. Treatment of in vitro cultured hMSCs can direct their secretome to favor tissue specific regeneration. Image courtesy of Dr. Nick Beijer.

Mesenchymal stem cell library

Building on the knowledge from the 90s biotech company IsoTis S.A., we established a library of hMSCs of over 300 different donors. Cells from many donors have been characterized for in vitro parameters such as proliferation and differentiation and for many donors we have established gene expression profiles and we have disclosed correlations between phenotypical features and gene expression.

Besides the traditional multilineage differentiation, we also have expertise in endothelial differentiation of hMSCs.

Scanning electron microscopical image 24 hours after seeding human bone marrow into a culture dish. Note the native rounded morphology and the sharply contrasting flattened colony-forming unit fibroblasts, referred to as mesenchymal stem cells. Image courtesy of Ruud Licht.

MosaCell scientific platform for patient-derived cells for therapy and disease modeling

cBITE founded the MosaCell initiative to unite scientists and clinicians working at patient-derived cells. MosaCell has three objectives: increase scientific exchange, sharing protocols and reagents and the establishment of the Maastricht Stem Cell biobank in which know how on MSC, IPSC and organoid culture will be centralized. More info at www.mosacell.com.

Further reading

• Candidate small molecule approach: Siddappa et al., PNAS, 2008
• Small molecule screen: Doorn et al., Biomaterials, 2012
• Mesenchymal stem cell bank: Mentink et al., Biomaterials, 2013 and Alves et al., PLoS One, 2012
• Endothelial differentiation: Portalska et al., PLoS One, 2012, Portalska et al., Tissue Eng Part A, 2013 and Portalska et al., Tissue Eng Part A, 2014