Organ replacement in the lab Organ-on-Chip: Micro-Organs for Personalised Cell Therapy

They fit in the palm of your hand – tiny mini-labs that researchers at Helmholtz Munich want to use to shape the medicine of tomorrow. “Organ-on-chip” is the key word. This approach combines engineering and biology, not only making it easier to research diseases and develop personalised treatment, but could also replace animal experimentation in the future.

The chip that Matthias Meier and his team at the Helmholtz Pioneer Campus are using to cultivate human stem cells and add them to functioning, tissue-like cell structures – known as organoids – is four centimetres by five centimetres. Their long-term goal is to develop personalised cell therapy for persons with obesity or diabetes.

Organ-on-chip combines microfluidics and stem cell technology on one platform. What does this mean exactly? Paper-thin fluid channels supply tiny cell culture chambers with nutrients and a wide range of semiochemicals. The chambers contain pluripotent human stem cells. These can be turned into any cell in the human body, depending on the semiochemicals that they come into contact with.

"With the organ-on-chip technology, we are gaining unprecedented insight into our own physiology. From the stem cell to the organ, we can clearly define the conditions and thus quantitatively document every molecule involved while also characterising previously undescribed processes and molecules."

- Matthias Meier

What exactly is organ-on-chip used for? The number of possible applications for micro-organs is immense. Starting with

• fundamental research and
• differentiation of the patient’s own stem cells for cell replacement therapy,
• to application for pharmaceutical development and
• toxicology

to test substances or determine whether substances may be harmful to human cells.

It is also possible in the lab to newly cultivate special cells from the patient’s stem cells that are destroyed by diseases, and to then use them for treatment in personalised cell replacement therapy.

This is precisely what Meier’s team is working on with Heiko Lickert, Director of the Institute of Diabetes and Regeneration Research (IDR) at Helmholtz Munich. Together they have developed a pancreas chip known as the PancChip. With this chip they hope to simulate the development of insulin-producing cells as accurately as possible in order to cultivate insulin-producing beta cells from patients’ stem cells for cell replacement therapy for type-1 diabetes.

Pancreas, beta cells, cell replacement therapy?! Let’s take a step back:

Diabetes mellitus is a common illness that almost everyone has heard about. It is also referred to as “sugar diabetes”, as it increases blood sugar content to dangerous levels.

Diabetes is not just a disease, but rather an umbrella term for various metabolic disorders. One of these is type-1 diabetes, which is an autoimmune disease (meaning that the immune system incorrectly attacks and destroys endogenous cells). Type-1 diabetes targets insulin-producing beta cells in the pancreas.

Insulin plays an important role in sugar metabolism. Without this hormone, body cells cannot integrate blood sugar, and blood sugar levels rise. If the immune system continues to destroy beta cells when type-1 diabetes is present, less and less insulin is dispensed into the blood until insulin production halts entirely.

There is not yet a cure for type-1 diabetes. Patients have to inject or pump insulin into their body for their entire life.

Cell replacement therapy – the replacement of destroyed beta cells with functional cells – has long been a focus of diabetes research. There are initial methods for transplanting healthy beta cells, but cells from deceased organ donors have been the primary source. The disadvantage here is that there is a short supply of these cells, and the recipients’ immune systems often reject these foreign cells.

The new PancChip from Meier and Lickert could solve this issue in the future, thereby creating new possibilities for treatment.

The researchers start out with induced pluripotent stem cells (iPS cells). These are made from previously developed body cells that are artificially returned to their stem cell state in the lab in a process known as reprogramming. Like real stem cells, iPS cells can essentially be indefinitely multiplied and converted into a wide variety of cell types. And because they are made from the patient’s own cells, the risk of rejection is lower because the patient’s body does not identify its own cells as “foreign”.

"With cell replacement therapy, we have a real chance at curing type-1 diabetes instead of just treating the symptoms."
- Heiko Lickert

The iPS cells are cultivated on the PancChip into insulin-producing cells in hundreds of small cell culture chambers. At the same time, the system fosters quality control because the researchers were able to identify a cell marker that, as early as the beginning of cell development, shows which cells will and will not turn into particularly effective beta cells. Disruptive cell types can thus be sorted out early on, which increases the number of well-functioning beta cells.

Before the PancChip can be used to treat people with type-1 diabetes, however, there are still some challenges for the researchers to overcome: Production has to be increased so that sufficient quantities of the new beta cells can be produced, and the method for transplanting the newly cultivated cells has to be optimised. Matthias Meier, Heiko Lickert, and their teams are working hard on these issues so that personal type-1 diabetes treatment can hopefully be facilitated soon.

Further research is focusing on many other uses of organ-on-chip technology, because they go far beyond the acquisition of new beta cells. With the organoids on the PancChip, the research teams can also generally examine the mechanisms that create diabetes or other diseases of the pancreas, such as pancreatic cancer – without any animal experimentation whatsoever.

Our researchers at Helmholtz Munich want to use state-of-the-art technology to overcome the past boundaries of science and shape the medicine of tomorrow, in a more patient-friendly and affordable manner.

Latest update: September 2022.