Molecular and Translational Regenerative Medicine

cBITE Department

Molecular and Translational Regenerative Medicine

The research group “Molecular and Translational Regenerative Medicine” led by Martijn van Griensven aims at further developing and innovating a competitive research line including translational aspects in the field of molecular and cellular regenerative medicine. More explicitly, the group centres its attention on understanding pathologies and (thereby) developing innovative therapies for defective organs or organ-systems, tissue-combinations and tissues using molecular cues, cell-derived structures and/or cell(s). To achieve this goal, state-of-the-art research will be performed investigating (stem) cell biology, cell-cell and cell-biomaterial interactions, molecular pathways, immune interactions, and patient-derived materials. This will result in better understanding of the pathogenetic pathways and lead to translational research from pre-clinical studies up to first-in-man and clinical studies. This research is warranted by integrating expertise in molecular/cellular biology and translational expertise with engineering and biomaterials science.

Many processes in the human body follow similar molecular schemes. The overall processes are similar; the actual specific “actors” may differ. For instance, micro-RNAs (miRNAs) were found to be involved in tumorigenic processes. In the course of further investigations, aberrantly regulated miRNAs were shown to be associated with many different pathologies. The specific miRNAs are different, but the overall concept is the same. Thus, it is of utmost importance to employ such platform technologies in the different aspects of regenerative medicine in our research group. We will use the obtained information regarding the up- and down-regulated miRNAs for modulating them in order to induce regeneration.

Another aspect of interest for our group are tissue combinations. In organisms, hard and soft tissue transitions exist. Regenerating them is challenging because of the mechanical incongruency. Biomaterial gradients including spatiotemporal cues are developed and tested in vitro and in vivo. Examples are the enthesis (ligament-/tendon-bone) and osteochondral constructs. Different cell types will be considered as co-cultures. Furthermore, immune aspects are taken into consideration as well for the translatability and regenerative capacity.

Funding sources

European Union - Horizon 2020
cmRNAbone – 3D Printed-Matrix Assisted Chemically Modified RNAs Bone Regenerative Therapy for Trauma and Osteoporotic Patients 
January 1, 2020 - December 31, 2023

cmRNAbone

Selected publications

  • Font Tellado S, Chiera S, Bonani W, Poh PSP, Migliaresi C, Motta A, Balmayor ER, van Griensven M. Heparin functionalization increases retention of TGF-β2 and GDF5 on biphasic silk fibroin scaffolds for tendon/ligament-to-bone tissue engineering. Acta Biomater. 2018; 72: 150-166, https://www.ncbi.nlm.nih.gov/pubmed/29550439
  • Kelch S, Balmayor ER, Seeliger C, Vester H, Kirschke JS, van Griensven M. miRNAs in bone tissue correlate to bone mineral density and circulating miRNAs are gender independent in osteoporotic patients. Sci Rep. 2017; 7(1): 15861, https://www.ncbi.nlm.nih.gov/pubmed/29158518
  • Seeliger C, Balmayor ER, van Griensven M. miRNAs Related to Skeletal Diseases. Stem Cells Dev. 2016; 25(17):1261-1281, https://www.ncbi.nlm.nih.gov/pubmed/27418331
  • Font Tellado S, Balmayor ER, van Griensven M. Strategies to engineer tendon/ligament-to-bone interface: Biomaterials, cells and growth factors. Adv Drug Deliv Rev. 2015; 94:126-140, https://www.ncbi.nlm.nih.gov/pubmed/25777059
  • Seeliger C, Karpinski K, Haug AT, Vester H, Schmitt A, Bauer JS, van Griensven M. Five freely circulating miRNAs and bone tissue miRNAs are associated with osteoporotic fractures. J Bone Miner Res. 2014; 29(8): 1718-1728, https://www.ncbi.nlm.nih.gov/pubmed/24431276

Image

The enthesis structure with reversed gradients of mineral and collagen that make up the 4 zones from the ligament/tendon to the bone. Especially, the hard-to-soft tissue transition is hard to regenerate.The enthesis structure with reversed gradients of mineral and collagen that make up the 4 zones from the ligament/tendon to the bone. Especially, the hard-to-soft tissue transition is hard to regenerate.
Bone formation modulating miRNA network including the possible target genes within the entire development line from mesenchymal stem cell to osteocyte.Bone formation modulating miRNA network including the possible target genes within the entire development line from mesenchymal stem cell to osteocyte.