Osteoarthritis is a degenerative joint disease that can cause joint pain and disability. This is indirectly caused by damaged articular cartilage. Regenerative cell therapies for damaged cartilage seem promising. However, remaining problems include limited chondrocytes availability and de-differentiation of these cells during 2D expansion. This can lead to fibrous repair tissue in cartilage defects, which lacks the mechanical properties of hyaline cartilage. Therefore, the LS-CarE consortium aims to engineer large scale cartilage implants. Human induced chondroprogenitor cells (hiCPCs) will be used for this, which will first be assembled into cartilage organoids and thereafter assembled into a larger tissue using biofabrication techniques.
This PhD projects focusses on finding a commercially viable method to create large quantities of high-quality cartilage organoids using mechanical stimulation, growth factors and matrix additives. It has been shown that assembling chondrocytes into organoids in a spinner flask with a matrix additive called notochordal cell-derived matrix (NCM), allows the cells to proliferate without de-differentiating. In this project, the use of immunologically inert chondroprogenitor cells, hiCPCs, to make organoids will be investigated. Using this off-the-shelf cell type will overcome the limitation of insufficient chondrocyte availability and the need for a biopsy to harvest cells from the patient. Furthermore, in this project, a replacement for the NCM will be explored. NCM is a porcine-derived matrix additive whose essential components are known. Using a proteomic analysis, the effector molecules in the NCM could be identified. A mixture of these matrix molecules and growth factors in a mechanically stimulated culture could potentially stimulate the organoid formation, proliferation and phenotypic stability of the cells. Finally, the organoid production will be transferred to a GMP-compliant system to scale up the process. The production of the hiCPCs and the biofabrication of the organoids towards a larger cartilage implant will be performed by external partners within the LS-CarE consortium.