Regenerative Medicine: Of Potency and New Organs (Part 1)

by Wiebke Heiss / MEDICA.de

From acute over chronic up to deadly diseases - there are a many problems to solve in medicine. Researchers have high hopes concerning stem cells and tissue engineering: Regenerative medicine will hopefully enable doctors one day to replace sick cells and organs with healthy ones.15/04/2009

Some have the power to do anything, others to do something and many have it to do just a few things: the equivalents in biology are called toti-, pluri- or multipotent stem cells. „These are cells that constantly renew themselves and are capable of differentiating in distinct cell types“, Thomas Skutella says. These cells are supposed to be the medical key to regenerate or replace malfunctioning parts of the body by, for example, generating dopamine producing cells for the brain of patients suffering from Parkinson's, insulin producing islet cells for the pancreas of diabetics or a new heart muscle to heal the pumping organ of heart attack patients.

The anatomy professor and director of the Center for Regenerative Biology and Regenerative Medicine at the university hospital in Tübingen, Germany feels certain that one day it will be possible to grow whole organs. „We obtained so much knowledge during the last century that we will in future be in a position to do so.“ However, there are still many obstacles to overcome such as to initiate the required differentiation in stem cells: Regarding the fact that a human body consists of more than 200 cell types, the technologies behind these processes are not perfect yet. „On one hand one needs the right factors to keep stem cells in their immortal state, on the other hand one requires stimulating factors to push them at the right moment into a certain direction“, Skutella explains. This is so far the only way to transform a progenitor cell into a muscle, heart or liver cell.

The all-rounder in action:
embryonic stem cells

Up to now embryonic stem cells have been regarded scientifically as being some kind of all-rounder – they are pluripotent and can develop into any known tissue. But they are also the centre of controversial debates regarding ethics and morality since they are obtained from human embryos being left over from in vitro fertilisation. Therefore, adult stem cells could provide an alternative beyond ethical controversies – as long as you reprogram them.

Morally defensible: adult stem cells

„Each human being has a certain potential for regeneration“, Skutella says. Thanks to adult stem cells - cells are present in different amounts in all organs - skin wounds can heal. However, these cells are at best multipotent which means that they can develop into different cell types of one lineage - a blood stem cell gives rise to blood and immune cells, a brain stem cell to the cell types occurring in the brain -, but it cannot differentiate into nearly all different body tissues.

The not so potent condition of an adult stem cell can be improved though by transferring the genes that renders an embryonic stem cell to be pluripotent. „The method is totally impressive because the biology behind it is so easy“, Skutella says. The result are induced pluripotent stem cells (iPS) which give new hope for stem cell research. The only drawback: researchers use viral vectors to bring in the genetic information and these are connected to a raised risk of cancer amongst other things. But Skutella does not doubt that „research will come up with technologies that enables us to reprogram cells without any danger to health.“ Which seems to prove true since meanwhile it has also been shown that harmless plasmids can be used in order to render adult stem cells pluripotent.

- Part 1: Of Potency and New Organs
- Part 2:
- 3. Teil: Man muss das Blut zähmen

Part 2: Potential in the Testis


Skutella and colleagues discovered an alternative last year: They found a premature stem cell source in men and have grown them successfully in culture. Next to embryonic stem cells these germ stem cells from the testis are the only cells that are existent in a pluripotent and not programed state. „We have known from the beginnings of stem cell research that germ stem cells are very potent“, Skutella says. However, they occur in very low numbers and it therefore took a long time to find them.

In order to investigate the whole potentials of the male germ stem cells, the German Federal Ministry of Research and Technology (BMBF) supports the Centre in Tübingen with half a million Euros. The goal is to develop pluripotent cell lines that remain stable for a long time and to characterise these. This monetary support is only one example for the cash that goes to the field of regenerative medicine in Germany for a good reason. In 2006, a BMBF-study showed that potential of this area in Germany: The study estimates a market potential of about 150 millions Euros per year for skin replacement products as well as cell therapies for repairing liver damages. It also predicts a greater market for the relatively young field of research concerning the heart like repairing damaged heart areas: The experts talk of more than a billion Euros turnover per year.

Money for renewing humans

That is one of the reasons why a reference centre concerned with cardiac stem cell therapy located in Rostock in East Germany is supported with 3,4 million Euros for a clinical study looking at the treatment of heart attack patients with adult stem cells. Also the German Research Foundation (DFG) participates with money within the framework of an excellence initiative and supports special centres such as the Centre for Regenerative Medicine in Dresden (CRTD) and Hannover (REBIRTH).

Also the Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO) at Hannover Medical School do research in the name of regenerative medicine. Next to stem cell research they also focus on tissue engineering in order to produce implants for the regeneration or the replacement of damaged organs. The methods comprise putting the patient's cells on a biological scaffold to grow a substitute for diseased or destroyed tissue such as heart valves or blood vessels amongst other things.

- Part 1: Of Potency and New Organs
- Part 2: Potential in the Testis
- 3. Teil: Man muss das Blut zähmen

Part 3: One Has to Tame the Blood


Also at the Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO) at Hanover Medical School research focuses on regenerative medicine. Stem cell research is being accompanied by methods concerned with tissue engineering in order to develop implants for the repair or replacement of damaged organs. Cells are being applied to a biological scaffold, a matrix structure, in order to culture a substitute for diseased tissue such as heart valves or vessels.

Christian Hess is a biologist at LEBAO and could lend a helping hand to millions of people suffering from lung diseases in Germany by working on the development of a bio-artificial lung. He and colleagues try to create an implantable bio-hybrid lung substitution system with the help of stem cells and biocompatible plastics - hoping for a system being able to take over lung function completely.

We copy from nature

The basis for the design is a ventilation system that can already supports the lung – a simple filtering apparatus that channels a patient's blood outside its body. A special membrane that is able to exchange gases is the point where carbon dioxide is extracted from the blood and oxygen in turn is delivered to it before the lifeblood returns into the body. „However, since the membrane is made up of plastics, the system can only be used for 30 days in a row", Hess says. The risk of developing a blood clot at the plastics-blood interface gets too high after this time period. Therefore, Hess took a close look at nature and then tried to simulate the conditions prevailing on the inner linings of a blood vessel – surroundings where clotting does not take place.

That is why the researchers are trying to create an environment for endothelial cells - cells normally lining the inner parts of blood vessels - to settle on the gas exchange membrane. These cells are being cultured from progenitor cells from cord blood or peripheral blood. „Our results so far make us look in the future positively“, Hess says. „The material is well suited, cells do settle on it on a small scale.“ Even though the whole investigation is still at its very beginnings it is theoretically feasible to think of a device that one day will support lung function permanently.

Wiebke Heiß
MEDICA.de

- Part 1: Of Potency and New Organs
- Part 2: Potential in the Testis
- Part 3: One Has to Tame the Blood