"Once we have found the factors by which body cells can be re-programmed into stem cells, then therapeutic cloning might become superfluous," said Hans R. Scholer, director of the Max Planck Institute for Molecular Biomedicine in Munster, Germany, at an international scientific symposium on stem cell research in Kobe, Japan.
From September 1 - 3, 2005, acclaimed stem cell researchers from around the world met at the RIKEN Center for Developmental Biology (CDB) to discuss the current status of their science. The workshop titled "Stem Cells in Reproduction and in the Brain" was held as part of the "Germany in Japan Year" 2005/2006 and was jointly organized by the Ernst Schering Research Foundation, the Max Planck Society and the RIKEN CDB.
"The fact that cell biology is becoming increasingly combined with molecular biology is a major step forward," Scholer explained. The co-organizer of the symposium drew his confidence from a series of lectures on the factors influencing the origin and the differentiation of stem cells.
Philippe Collas of the University of Oslo, Norway, for example, succeeded in converting human skin cells back into a multi-potent stage with an extract mixture of pluri potent embryonic carcinoma cells. Jeong Tae Do of the Max Planck Institute in Münster showed that even differentiated body cells can be re-programmed into embryonic stem cells. He merged brain cells from mice with embryonic stem cells. The result was a hybrid cell with a quadruple set of chromosomes. The cells did not differ from normal embryonic stem cells with regard to their molecular biological behavior.
Other researchers are finding the key to the opposite path: They are searching for substances that contribute to the differentiation of stem cells.
Thus Tomohiro Kono of the Tokyo Agricultural University, Japan, presented the creation of mice through the union of two egg cell nuclei - in contrast to natural fertilization where nuclei from egg and sperm are combined. In doing so, Kono hopes to decipher the molecular mechanisms underlying imprinting. He showed a method for converting maternally imprinted genes to genes that can basically behave as paternal types, thereby succeeding in generating a living parthenogenetic mouse.
Shin-Ichi Nishikawa, Deputy Director of RIKEN Center for Biological Development and co-organizer of the symposium presented studies of the so-called "Notch gene", which helps to maintain melanocyte stems cells in hair follicles alive. Its over-expression, however, can become dangerous as it induces the increased formation of pigment cells and so could contribute to the development of a melanoma.
Nishikawa praised the good cooperation of the three institutions/foundations that jointly organized the workshop: "Our RIKEN Institute has been successfully collaborating with the Max Planck Society for a long time." The cooperation with Schering has also become important since the Berlin-based pharmaceutical company opened its research center in Kobe in 2004.
"The RIKEN CDB was one of the reasons why we located our Japanese research center in Kobe," emphasized Günter Stock, symposium president and member of the Board of Executive Directors at Schering. "The Germany in Japan Year" offered a good opportunity to showcase the common interests in stem cell research that Max Planck Society, RIKEN, and Schering have with a joint workshop." Regenerative medicine is currently one of the most exciting areas of modern medicine, Stock stated. He asserted: "In the last15 to 20 years we have found substantial factors that can stimulate adult stem cells to self-heal the body."
Two other sessions emphasized the role of stem cells in reproduction and the nervous system. "Both are very exciting areas in which many unexpected phenomena have been reported", said Shin-Ichi Nichikawa.
In one of the highlights, Shin-Yong Moon of the Seoul National University, Korea, presented the experiments on obtaining the first human stem cell lines by cloning. "These cell lines are not suitable for transplanting into human beings," he explained. At this time, he and his colleagues are focussing their research efforts on the fundamental principles of cell development in order to gain a better understanding of diseases. "There are still many hurdles to overcome before they can be used for treatment."
Max Planck researcher Scholer and Mitinori Saitou of the RIKEN CDB are exploring the development of female germ cells. Scholer demonstrated how embryonic mouse cells can differentiate into egg cells in cell culture. Here lies "the potential to treat infertility in women someday." Saitou is investigating the molecular biological switches that trigger germ cell formation in the body.
Yuichi Niikura of the Harvard Medical School in Boston then refuted the belief that women cannot generate new egg cells because there is no self-renewal of stem cells in mature ovaries: "We believe that germ stem cells are present in bone marrow." When needed, they would migrate to the ovaries and differentiate into new egg cells. This result could also become of great clinical importance one day, perhaps for treating infertility in women after cancer treatment.
Experiments with nervous system stem cells are already one step closer to clinical development. Steve Goldman of the University of Rochester, USA, is exploring neuroglial stem cells. This nerve-protecting insulation layer is destroyed in many serious diseases such as multiple sclerosis. Goldman isolated neural stem cells from the brains of accident victims and cultivated the precursors to glial cells. He transplanted them to a mouse model that cannot produce myelin, a nerve insulating substance made by glial cells. In this manner, he succeeded in completely repairing the insulation layer of certain nerves.
Hideyuki Okano of the Keio University in Tokyo, Japan, intends to treat paraplegias. He showed that a commercially available antibody is able to suppress the inflammation that occurs in connection with spinal cord injury and in doing so supports nerve regeneration. The first studies on humans are already planned.
Hans R. Scholer was full of eagerness when he closed the meeting: "The best meetings are those at which one can hardly wait, for sheer excitement, to get back to the laboratory - and this was one of them" he said.