News

Published: 10 August 2023

Detailed laboratory procedures show the interaction of human cells in healthy and diseased condition

Despite intensive research and high investments in research projects based on animal experiments, clarification on how the interaction of cells works in organs or on a smaller organizational level is still pending. However, this knowledge is crucial: the only way to find out about disease development is by comparing a sick organism’s reaction to the reaction of a healthy one – among other things, this is the basis for developing effective drugs. Complex analyses are used to create so-called cell atlases based on human data, which can show what happens when healthy cells develop into diseased cells.

An increasing number of projects are oriented towards humans, i.e. they work with human cells and/or data and develop specific methods and models that reflect the human situation as precisely as possible. Keeping an organism functional and healthy is a highly complex interaction of countless factors at various levels such as DNA, protein, and cell level, Interactions in restricted cell areas, within organs, and between organs also play an important role. Moreover, there are many different, very specific factors that trigger a disease. This usually starts in individual cells, which is why there currently are projects investigating exactly this. A cell atlas is a platform that maps (all) the cells of the human body. (1)

Both the Human Cell Atlas (HCA) project (2) and the Human Biomolecular Atlas Program (HuBMAP) (3) aim to use a network of different researchers around the globe to characterize every cell in the healthy human body in order to determine its function and its interactions. This should be mapped into a 2- or 3-dimensional "plan". The basis usually are human tissues obtained from voluntary donors or through medically necessary biopsies or surgeries. These cells are characterized using various analysis methods. In the process, data is obtained, e.g. on the genetic information DNA and its transcription into RNA, the entirety of all proteins that are present in the respective cell, and also all substances relevant to metabolism such as types of sugar, amino acids, or fats. These individual cells are then spatially classified, so that it can, for example, be determined where a specific cell is located within the organ. Within an organ, cells often organize themselves into microstructures and influence each other’s functions.

One publication (4) focused on kidney disease: researchers characterized and compared data from 45 healthy donor tissues with diseased tissues from 48 patients. They found 51 different main cell types and also discovered previously unknown cell populations. In addition, 28 different conditions at the cellular level that are altered in kidney diseases could be identified.  Furthermore, processes that play a role in injury and repair have been identified. These results are also relevant for the Kidney Precision Medicine Project (KPMP), which follows a similar approach to the human atlases but focuses on kidney diseases (5).

Another publication (6) examines previously unknown mechanisms at the interface between the fetus and the maternal placenta. The maternal blood vessels that supply the fetus are remodelled in a mechanism – not yet understood - that originates from the fetal tissue, so that an optimal supply of nutrients can take place. Since these mechanisms are highly specific, they cannot be simulated in animal experiments. Now, using data obtained from the tissues of 66 human samples, many details of this interaction and the mutual influence of different cells and immune system components could be elucidated. For this purpose, data of half a million cells was evaluated.

Furthermore, in another research project (7), a detailed cell atlas of the intestine was created, in which not only important organization of the various immune cells was determined, but also new secretory subtype cells were discovered. Here the cell atlas of a healthy condition serves as an important reference for comparing and researching disease mechanisms as well as for developing therapies on that basis.

This information provides an important - perhaps the most important - basis for researching countless diseases and thus creating the basis for therapies and drug development. There are still many cells and organs to be studied and mapped in the near future, so more exciting, new, and important insights can be expected. The decisive advantage is that human tissues or cells are used, and the development of the disease is thus examined in the right species.

References and further information

1. Nature News Cell ‘atlases’ offer unprecedented view of placenta, intestines and kidneys >>
2. Human Cell Atlas (HCA) HCA Data Portal: Dataportal >>
3. The Human BioMolecular Atlas Program (HuBMAP) Website >>
4. Lake B. et al. An atlas of healthy and injured cell states and niches in the human kidney. Nature 2023; 619(7970):585–594
5. Kidney Precision Medicine Project Website >>
6. Greenbaum S. et al. A spatially resolved timeline of the human maternal–fetal interface. Nature 2023; 619(7970):595–605
7. Hickey J. et al. Organization of the human intestine at single-cell resolution. Nature 2023; 619(7970):572–584