Organoids with vessels

In 2006, Japanese scientists invented a new way to create pluripotent stem cells through epigenetic reprogramming of connective tissue cells. Their discovery led to the emergence of a very valuable type of cells that can be used to grow any cells of the human body.

When cultivating these so-called induced pluripotent stem cells (iPS cells) in the form of three-dimensional cellular aggregates, by selectively adding growth factors, functional miniature versions of organs, so-called organoids, can be created. In recent years, this technology has been used, for example, to create models of cell cultures of the intestine, lungs, liver, kidneys and brain.

Such organoids are often surprisingly similar to real tissues. However, most of them remained incomplete due to the absence of stromal cells and life-supporting structures. For example, there were no blood vessels and immune cells in the tissues. In the process of embryonic development, all these structures are involved in the process of constant exchange, they influence each other and thereby contribute to the development and maturation of a tissue or organ. Diseases also usually develop in a tissue context involving various cell types. Therefore, the selective inclusion of stromal components, and especially functioning blood vessels, will contribute to the maturation of already existing organoid models.

Scientists from the University of Würzburg have taken an important step towards the development of such complex organoids and created so-called mesodermal progenitor cells from pluripotent stem cells. Under the right conditions, such progenitor cells are able to create blood vessels, immune cells and connective tissue cells.

To demonstrate the potential of mesodermal progenitor cells, scientists mixed them with tumor cells, as well as with brain stem cells that were previously obtained from human iPS cells. This mixture grew in a Petri dish into a three-dimensional organoid of a brain tumor with functional blood vessels, connective tissue and brain-specific immune cells, the so-called microglia. The vessels in the tumor organoid are connected to the host vessels after transplantation. It is also noteworthy that mesodermal progenitor cells deliver microglial cells to the nerve tissue.

Organoids have an amazing similarity with real embryonic tissues. In the figure from left to right: 3D reconstruction of the vascular network inside the organoid; brain organoid with blood vessels (red) and brain stem cells (green); organoid tumor with blood vessels (red) and tumor cells (green). In the future, organoids created with the help of new technology will help scientists shed light on the processes associated with the genesis of diseases and analyze in more detail the impact of therapeutic methods before using them.

This would reduce the number of animal experiments. In addition, organ models can contribute to a better understanding of the processes of embryonic development and will allow growing tissues that can be effectively transplanted, since they already have a functional vascular system.

Article by Wörsdörfer et al. Generation of complex human organoid models including vascular networks by incorporation of mesodermal progenitor cells is published in the journal Scientific Reports.

Elena Panasyuk, portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Universitat Wurzburg: Complex organ models grown in the lab.