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Sept. 17 press conference on advances in cell, tissue and organ transplantation

3 sections of the Transplantation Society to unite for the first time

On Monday, September 17 at 12:30 p.m. CDT, Dr. Megan Sykes, Dr. James Shapiro and Dr. Jacques Tremblay, presidents of IXA, IPITA and CTS respectively, will hold a press conference at the Hyatt Regency Minneapolis in Minneapolis, MN to summarize the groundbreaking research and recent advances made in the areas of pancreas, islet, cell and transplantation and xenotransplantation (the transfer of animal cells into humans). The speakers’ credentials are as follows.

• Bernhard J. Hering, M.D., Professor of Surgery, Director of Islet Transplantation, Eunice L. Dwan Diabetes Research Chair, Scientific Director, Diabetes Institute for Immunology and Transplantation, University of Minnesota, Joint Conference President and Press Conference Moderator.

• Megan Sykes, M.D., Harold and Ellen Danser Professor of Surgery and Medicine (Immunology) and Associate Director, Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, IXA President and Joint Conference Scientific Program Chair.

• A. M. James Shapiro, M.D., Ph.D., Professor of Surgery, Wyeth-Ayerst Canada/CIHR Clinical Research Chair in Transplantation and Director of the Clinical Islet Transplant Program, University of Alberta, IPITA President.

• Jacques P. Tremblay, Ph.D., Professor, Université Laval and Centre Hospitalier Universitaire de Québec, CTS President.

Key findings from the research will be further addressed through more than 130 invited presentations and 474 submitted abstracts during the Joint Conference, which will take place Saturday, September 15 through Thursday, September 20.

“The extraordinary support we have received from IXA, IPITA and CTS has allowed us to create a forum of the highest scientific merit that offers scientists, physicians, surgeons, nurses, organ procurement personnel and pharmacists the opportunity to interact with the world’s most distinguished thought leaders in cell and organ transplantation,” says Joint Conference President Dr. Bernhard Hering. “Ultimately, the Joint Conference will contribute to enhanced care for transplant recipients, and consequently result in the increased utilization of transplantation for the treatment of diabetes, heart, lung, kidney or liver failure, muscular dystrophies, neurodegenerative disorders and other indications.”

From animals to humans

Sykes, who will speak at the press conference on behalf of IXA – an organization that promotes the scientific aspects and ethical conduct of xenotransplantation, which is the transplantation of cells, tissues and organs from animals to humans – about tolerance, a state in which the immune system regards the donor organ as self, so that it is accepted without requiring long-term immunosuppressive therapy. “For the first time, tolerance to organ allografts has been intentionally achieved in humans using an approach termed ‘mixed chimerism’, which was first developed in animal models,” Sykes explains. “This approach also has been shown to achieve xenograft tolerance in animal models.”

Sykes adds that the mixed chimerism approach may be most effective when combined with thymic transplantation to achieve tolerance of all major components of the immune system (“innate” and “adaptive”) that resist xenograft acceptance.

Other major advancements in xenotransplantation that Sykes will address are as follows.

• Advances in genetic engineering have made the generation of multiple genetically modified pigs possible, inhibiting antibody-induced rejection, cellular immune responses and coagulation pathways that promote rapid xenograft rejection.

• Genetic engineering and pig screening to reduce the infectious risk of xenotransplantation.

• The development of genetically modified pigs has heart graft survival exceeding 100 days in non-human primates.

• The use of thymic transplantation to induce tolerance to pig antigens has resulted in lasting kidney graft survival from genetically modified pigs in non-human primates.

• Long-term pig islet graft survival has been achieved in non-human primates using new immunosuppressive agents.

• A key pathway has been identified that prevents macrophages from destroying cells and does not function in the pig-to-human combinations. This work may allow the development of pigs whose cells are resistant to destruction by human macrophages.

Pancreas and islet transplantation
Shapiro, who will represent IPITA at the press conference, plans to provide an update on clinical islet transplantation, with an emphasis on the opportunities and challenges that lie ahead. His presentation will include the major challenges the organization faces with pancreatic digestion enzymes.

Additionally, Shapiro will cover the following topics.

• More than 600 islet transplants worldwide have been completed in the past seven years.

• About 100 islet transplants that took place during the past seven years were done through the Clinical Islet Transplant Program.

• Single donor islet transplants have been successful at some centres.

• There are some issues with long-term islet dysfunction that are not fully understood.

Cellular transplantation
Tremblay, who speak at the press conference on behalf of CTS, says that cell transplantation is a possible treatment for several hereditary and acquired diseases. Highlights from his presentation are as follows.

Autologous cells may be used to repair the same type of tissue from which they originated. For example,

• Muscle stem cells (called satellite cells) may be obtained from a thigh muscle biopsy, expanded into a few million myoblasts and transplanted into the urinary sphincter to treat urinary incontinence due to stress.

• Cartilage cells called chondrocytes may be used to repair cartilage damaged following an injury.

• An artificial liver has been produced to treat liver failure in animal models.

Cells may also be used to treat another tissue that the one they originated from. For example,

• Skeletal muscle precursor cells (i.e., myoblasts) have been transplanted in the heart of patients following an infarct to prevent the development of heart insufficiency. The results obtained are encouraging.

• Bone marrow stem cells have also been injected into the heart to prevent heart insufficiency.

It is also possible to use pluripotent stem cells derived from adult tissues and transform them into other types of cells to treat different tissues. For example,

• Stem cells extracted from the bone marrow or from the adipose tissue have been used to repair muscle fibers.

• Stem cells extracted from the muscles of the skin have formed neurons, which may be eventually used to treat Parkinson disease.

• Stem cells extracted from muscles have been used to repair bones and cartilage.

Of course, various types of cells (presumably all types of cells) can be obtained by the differentiation of embryonic stem (ES) cells. For example,

• Cardiomyocytes can be obtained from ES cells and are currently being used to repair hearts in animal models. Muscle precursor cells can also be obtained from ES cells. Other groups are trying to form neurons and islet cells form ES cells.

The use of ES cells will require either some immunosuppression to prevent rejection or will require therapeutic cloning to make them genetically identical to the patients. This last approach is currently not permitted in most countries. However, scientists in England have recently been allowed to transfer human nuclei in ES cells derived from animals.

Gene therapy may be used to treat a variety of genetic diseases by introducing a normal gene with viral vectors. However, gene therapy may also be done by using cells as a vector to introduce normal genes. For example,

• The transplantation of myoblasts obtained from a normal healthy donor can restore the expression of dystrophin in the muscle fibers of Duchenne Muscular Dystrophy patients. A second clinical trial is under way to verify whether this treatment can increase the strength of one muscle.

The transplantation of cells obtained from another person requires a sustained immunosuppression. This requirement is already being avoided in animal models by inducing immunological tolerance. An alternative method to avoid the use of an immunosuppressive treatment is to genetically correct the own patient cells in culture. Again, this has already been achieved in animal models. Such ex vivo gene therapy avoid the problem of immune responses recently observed following the direct delivery of gene with viral vectors such as adenovirus and AAV.

Organ transplantation currently is a routine method to treat many organ failures. Because of organ shortage, in the future transplantation of normal or genetically modified cells will be more frequent than organ transplantation because it could repair organs before their failure and even correct genetic diseases.

For more information about the 2007 Joint Conference, visit www.cts-ipita-ixa-2007.org. Contact Molly Kersten (mkersten@r-p.com) to attend the press conference on Monday, September 17.

About The Transplantation Society
The Transplantation Society is an international forum for the world-wide advancement of organ transplantation. Headquartered in Montreal, QC, Canada, the organization aims to provide the focus for global leadership in transplantation, development of the science and clinical practice, scientific communication, continuing education, and guidance on the ethical practice. For more information about The Transplantation Society, visit www.transplantation-soc.org.

About IXA
The International Xenotransplantation Association (IXA) was established in 1998 to promote the advancement of the science and the responsible conduct of xenotransplantation research. Its major activities include a biannual scientific congress and the dissemination of information to the scientific community and public about scientific advancements made in xenotransplantation. For more information about IXA, visit www.transplantation-soc.org. Megan Sykes, M.D., Harold and Ellen Danser Professor of Surgery and Medicine (Immunology) and Associate Director, Transplantation Biology Research Center, Harvard Medical School, serves as the current IXA President and Joint Conference Scientific Program Chair.

About IPITA
The International Pancreas and Islet Transplant Association (IPITA) is a scientific forum for the exchange and discussion of clinical and experimental results and experiences relevant to transplantation of insulin-producing tissue in the treatment and cure of diabetes mellitus. For more information about IPITA, visit www.ipita.org. A. M. James Shapiro, M.D., Ph.D., Professor of Surgery, Wyeth-Ayerst Canada/CIHR Clinical Research Chair in Transplantation and Director of the Clinical Islet Transplant Program, University of Alberta, is the IPITA President.

About CTS
The Cell Transplant Society (CTS) is an international non for profit, incorporated collegial association of scientists with background and/or interest in the field of cellular transplantation.
The organization exists to promote research and collaboration in cellular transplantation. The research interests of members include pancreatic islets, bone marrow, endothelial, epidermal, myoblast, neural and stem cells. Investigators of cell and tissue transplantation share problems and research targets on topics such as separation techniques, culture methods, cryopreservation and banking, pretransplant immuno-modulation, micro-and-macroencapsulation, bioartificiality, tolerance, xenografts, quality control, implantation sites and techniques, experimental and clinical transplantation and gene therapy. For more information about CTS, visit www.celltx.org. Jacques P. Tremblay, Ph.D., Professor, Université Laval and Centre Hospitalier Universitaire de Québec, is the CTS President.

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