Complex Organoids From Stem Cells

Dr Wörsdörfer: “We believe that our tissue models are “superior” to many organoids that have been grown from stem cells in the lab before, as they contain the supportive framework of tissues, so-called stroma. Stroma, the connective tissue, consists of mesenchymal cell types and blood vessels, for example. So far, methods for the generation of organoids mostly focused on the parenchyma, which is the “functional” part of the organ.”

“Incorporating stromal components is of interest because tissue development requires multilineage communication, which means that several cell types communicate with each other to induce further differentiation steps boosting tissue maturation. It has been shown that during liver or lung development, such kind of communication is necessarily required.  In particular, stromal cells (mesenchymal cells, cells of the vessel wall) and the parenchymal cells (lung epithelial cells, hepatocytes) are involved in this process. We expect that organoids including the stromal compartment will be more mature regarding structure as well as function.”

“Similar to tissue development, disease development and progression also happens in a tissue context involving several cell types. For that reason, we believe that organoids including stromal components are better models to study disease mechanisms and also for drug screening applications. In addition, the growth of organoids in the lab is limited by a proper supply with oxygen and nutrients. This is because the tissue structures rely on supply via simple diffusion from the culture medium. This results in large areas of cell death in the organoid centre. Functional vascularisation will be the key to solve this issue.”

“And finally, the transplantation of lab-grown tissue patches requires a fast connection to the host vascular system to ensure supply of the tissue. Prevascularized tissue patches are required to make transplantation efficient and avoid death of the graft.”

“The next steps will be to connect the lab-grown vascular network to a circulatory system and to find out if this will firstly improve vessel maturation, and secondly allow vascularized organoids to grow to larger sizes and reduce cell death. Moreover, we will investigate the impact of the stromal compartment on the parenchymal compartment and try to model diseases in our improved organoids. In addition, we will further investigate the contribution of tissue resident macrophages. These cells of the immune system are also generated from mesodermal progenitor cells and can be found in our organoid models.”

“We will first continue with the brain organoids as they are already established in the lab.  Moreover, we are also interested in other tissues such as the heart.”

Speaking in regards to the expected path towards the commercialisation of the work Wörsdörfer responded by saying, “Our focus is basic research. We try to understand mechanisms of human embryonic development and disease. However, we of course see the potential of organoids especially with regard to disease modelling and drug screening applications. Moreover, mesodermal progenitor cells are an interesting cell source for bioprinting applications.”