17. October 2007 16:14
Stem Cell Research Marches On
Stem cell research proceeds apace, but many challenges lie ahead
Significant strides are being made in fundamental stem cell research in laboratories across the world, but many hurdles remain to be overcome before stem cells are routinely used to treat diseases.
This was one of the main messages to emerge from an international meeting of stem cell biologists held in Milan (30 Sep – 2 Oct, “Challenges in Stem Cell Differentiation and Transplantation”) and organised by the European Science Foundation’s EuroSTELLS programme in conjunction with one of ESF’s Member Organisations, the National Research Council (CNR) of Italy.
Stem cell therapy promises to open up a new way to treat diseases by growing new tissues and organs from stem cells – ‘blank’ cells that have the potential to develop in many different types of cell, also known as ‘toti-’ or ‘pluripotent’ cells. Stem cells exist in many tissues of the body, constantly replenishing dying cells, but cells that have most potential are those derived from embryos. The EuroSTELLS programme aims to develop a stem cell ‘toolbox’ by generating fundamental knowledge on stem cell biology.
The conference in Milan heard of many significant advances in the field. Dr. Michel Pucéat of the French National Institute of Health and Medical Research (Inserm) described promising new results in the use of stem cells to treat damaged heart tissue in animal models . Embryonic stem cells were first treated with a special compound known to prime the cells into becoming heart muscle cells. The cells were then seeded onto damaged heart tissue, where they proceeded to develop into heart muscle cells and restore some of the cardiac function.
Professor Ernest Arenas, a EuroSTELLS collaborator at the Karolinska Institute in Stockholm explained how stem cells could be used to treat Parkinson’s disease, which is characterised by the loss of a particular type of brain cell called dopaminergic neurons in the part of the brain called the substantia nigra. There has been some success in treating the disease by transplanting cells from foetuses into the brain, but, as Professor Arenas said, “One of the big problems with this kind of transplantation is availability of tissue. We need to get better material for transplantation and I think everyone agrees nowadays that the material will be stem cells.”
Professor Arenas’s research group has identified a particular class of protein molecules, called the Wnt family, which can coax stem cells into becoming dopaminergic cells, and when these cells are transplanted into the brain tissue of animals that have a condition similar to Parkinson’s disease, there is a significant restoration of the brain’s function .
Dr. Gianvito Martino of the San Raffaele Hospital in Milan pointed out that it is often difficult to integrate new cells that have derived from stem cells into existing tissues – a problem that is particularly significant with adult stem cells. Nevertheless, the new cells can still exert a profound influence on the existing neighbours – a so-called bystander effect.
Dr. Martino’s team has been working with a type of cell called adult neural precursor cells which, interestingly, possess significant immunological characteristics making them resemble immune cells. One effect of this is that when injected into a body, the cells automatically home in on inflamed tissue. In multiple sclerosis, for example, the cells find their way to damaged nerve cells and, through the bystander effect, induce the cells to repair themselves .
Dr. Maddalena Mastrogiacomo of the University of Genoa in Italy is investigating new ways of growing bone tissue from bone marrow stem cells, by using novel mineral scaffolds. When the porous scaffold, based on calcium phosphate, is seeded with the cells, the cells differentiate into bone cells and permeate the scaffold, gradually absorbing the mineral so that eventually the entire structure consists solely of new bone .
Professor Giulio Cossu of the San Raffaele Hospital in Milan described how certain cells called mesangioblasts have the ability to cross the walls of blood vessels and then differentiate into muscle tissue. This is significant because in muscle-wasting diseases there is so much muscle to replace that it would be extremely difficult to inject new cells into every affected area. Professor Cossu’s team has taken mesangioblast cells from dogs that have muscular dystrophy, used genetic engineering to correct the defect responsible for the disease, then administered the engineered cells to the dogs. The treatment produced significant alleviation of the symptoms .
As well as working directly on models of human diseases, many researchers around the world are experimenting with fundamental but vital aspects of stem cell biology to assemble the appropriate tools to allow research to proceed efficiently. A striking example of this was presented by Professor Joseph Itskovitz-Eldor, of the Rabam Medical Centre in Haifa, Israel.
“To fulfil the promise that stem cell therapy offers, an unlimited supply of cells cultured in completely defined and controlled conditions is required,” Professor Itskovitz-Eldor said. Conventionally, stem cells are grown on flat plates, but the Israeli researchers have devised a way of growing the cells in suspension in a three-dimensional culture. “We can switch from three-dimensional to two-dimensional culture and the cells will still grow nicely,” Professor Joseph Itskovitz-Eldor said. “Experiments have shown that the cells retain their viability and integrity, and we think we can have unlimited numbers of undifferentiated human embryonic stem cells in defined conditions.”
Balanced against the advances in research, some problems stubbornly persist. In particular scientists would like to develop embryonic stem cell lines derived from large animals such as the pig, sheep, horse and cow.
As Professor Cesare Galli, a EuroSTELLS researcher in the Laboratory for Reproductive Technology in Cremona, Italy, explained, “Large animal models will provide models that are closer to the human than the rodent models we currently have. However, bona fide stem cells in large animals are still elusive and we have not got the right conditions to keep them going.”
Dr. Irena Vacková, of the Institute for Animal Science in Prague, has been attempting to develop an embryonic stem cell line from the pig. “The pig is a very good animal model for humans because it is physiologically and immunologically similar,” she said. “But it has proved impossible so far to establish a stable line of porcine embryonic stem cells.”
The overall picture of stem cell research was best summarised by Professor Inder Verma of the Salk Institute in the US, who said, “There must be a certain degree of caution in the way we portray these technologies. I believe the technology really is there, and there is a lot of exciting potential. We are making improvements – although we still need to know a lot about the way that these cells are regulated in the body and about any immunological consequences. There has been substantial progress over the last 20 years, but it is important to bear in mind that these things take time. As successful as these technologies may become there is still a long way to go.”
EuroSTELLS is the European Collaborative Research (EUROCORES) programme on “Development of a Stem Cell Tool Box” run by the European Medical Research Councils (MED (formerly EMRC)) Unit in the European Science Foundation. ESF provides scientific coordination and support for the networking activities of funded scientists through the EC FP6 Programme, under contract no. ERAS-CT-2003-980409. Research funding is provided by the participating national organisations.
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