Human organs cell by cell from a laboratory

In the future, our own cells can be used for growing tissue and perhaps even whole organs to replace damaged ones. A research group in Oulu disassembles a kidney and reassembles it for better understanding of the process by which organs form.

It may become possible to grow organs from a person’s own cells within the next decades. There were news reports in early 2016 on 3D printed body parts which have grown a vascular system in animal models. New stem-cell technologies make it possible to grow human tissue as well.

”The organ production process is a big issue in medicine, a real megatrend. Researchers have developed, for example, various growth factor cocktails, which can be used to produce cells and steer them to certain kinds of development”, describes Professor in Developmental Biology Seppo Vainio.

"The kidney is a good model for studying organ generation and delopment questions on a general level", says Professor Seppo Vainio, holding a 3D printed plastic kidney.

Professor Vainio and his research group study the methods of differentiation of tissues and organs, and they develop new techniques for experimental modelling of illnesses, for example. The group focuses on kidney and skin research.

”The kidney is a good model for studying these developmental questions on the general level. Same methods can be applied to other organs as well, such as skin, pancreas and heart”, says Vainio.

There are many lines of research related to growing an entire organ, such as utilization of organ printing and biomaterials. Vainio demonstrates a model of a kidney manufactured from plastic with a 3D printer, and says that with optical imaging we are already able to make accurate 3D models of tissue and entire organs.

”When we learn to grow seed cells which grow an organ, we can then use a 3D map of the organ to print biomaterial produced by the cells, such as functionalized nanocellulose, organ seed cells or matrix, into the right places to make a biotechnically generated organ.”

From mouse models to human cells

A turning point in the development of cell and tissue technology happened some ten years ago, when cultivated human cells were used to produce pluripotent stem cells, iPS cells. For example, an adult human’s skin cell can now be reprogrammed into a heart muscle cell.

”Previously we could do gene targeting only in embryonic stem cells. Therefore research was primarily based on using test animals, as human embryonic stem cell research is controversial. Now we can generate cells similar to human embryonic stem cells in an ethically sustainable way”.

Organ cultivation methods make it possible to follow the forming of an organ in a laboratory in real time and very closely.

It is possible to model human diseases in mice, but an animal model never fully corresponds to the human. With iPS cells we can research disease mechanism in human cells, or develop new kinds of treatment to meet the individual’s needs. iPS cells generated from a patient’s own cells make it possible, for example, to replace damaged cells with transplants with no major risk of rejection.

Mouse research is still in a central role in researching the formation of a real organ. With organ cultivation methods we can follow the formation of an organ in a laboratory in an undisturbed situation very closely, cell by cell.

”This gives us information that can be used in programming pluripotent cells. With knowledge of organ cultivation we try to replicate the generation of organ structures in organoids, 3D cell cultures grown from stem cells. Stucture similar to that of the kidney has also been produced”, says Vainio.

Shape still a mystery

The research is constantly advancing, but many central questions remain unsolved. Safety of stem cell methods must be thoroughly studied. Skin cells only have a certain part of the genome’s program in use. When the gene is activated, mutations may also occur.

”We must use screening to find those cells more efficiently, where no mutations have occurred. However, there seems to be some repairing going on in the reprogramming of the cell, as if in a reboot of a computer”, says Vainio.

It is also still a big mystery how an organ gets its shape.

”In nature, everything has its function, and shape is related to it. There is a physical reason for the kidney’s particular shape. However, we do not yet know for sure what regulates the shape and how the generation programs of organs originate”, explains Vainio.

Organ like a ball pool

Nowadays all genes that are primarily located in the kidney are known, and thousands which participate in shaping the kidney have been identified.

Vainio and his research group have studied the formation process of blood vessels in the kidney by removing entire cell types instead of genes. This way the stem cell which created the entire vascular system was identified.

It is also possible to remove or return the nephron, the central filtering unit in the kidney, by using equivalent techniques. Vainio makes an analogy to a children’s ball pool: we can remove all blue balls or replace them with green ones, and see what happens.

”We are one of the leading research groups in the world in that we can explode an organ. We can bring the organ embryo to its singular cell stage, and then bring the organ back together. This way we can research the functions of hunderds of genes or any cell in the organ”, Vainio says.

Nature is helping the researchers here. Cells are so intelligent that they can fine-tune the structure, and form the organ.

”Cells have some kind of a spatial memory. It is remarkable that cells can even be frozen, and they still remember the shape”, says Vainio.

Vainio does note that it is not necessary to duplicate nature as such.

”Key cell types of an organ may even be located in some other organ and form a kind of multiorgan formation. We are sure to encounter different kinds of solutions.”

 

Text: Heidi Hahtola

Profile: Tiina Pistokoski

Picture of a kidney and video of kidney formation: Research group of Seppo Vainio

 

Individual treatments from iPS cells

  • Induced pluripotent stem cells ie. iPS cells can be generated from skin cells or blood cells by activating certain genes. The cells can be directed to differentiate in a preferred direction.
  • The advantage of iPS cells is that they do not require embryos to form, and they are genetically identical with the patient’s own genome.
  • The stem cells of an adult human are already being used in treating leucemia, for example.
  • iPS cells can be utilized in modeling diseases, developing individual highly selective drugs,  and even in replacement treatments of cells and tissue.

Last updated: 1.11.2017