Stem Cells Reloaded

Derek A. Persons, M.D., Ph.D.

Today, a sequel to the programs on the topic of stem cells from yesterday will be offered in the way of an Education Session that will delve into the topic of stem cell mobilization and a Scientific Committee Session which will explore the science and ethics of creating optimal stem cell donors through embryo selection.

In the Scientific Committee Session on Transplantation Biology (7:30 a.m. – 9:15 a.m.) chaired by Dr. Stephen J. Forman, presentations will center on reviewing the technological ability as well as the ethical considerations of using pre-implantation genetic analysis of human embryos to select those with the potential to serve as a matched hematopoietic stem cell donor upon birth. Dr. John E. Wagner will review his group’s experience using in vitro fertilization and embryo screening to generate a sibling stem cell donor for children with lifethreatening hematopoietic disorders. This approach entails generating embryos and screening them for HLA genotype and genetic disease status. From this process, an HLA-identical, disease free embryo is identified for in utero implantation and upon birth, umbilical cord stem cells can be collected and used to treat a disease affected sibling. Thus far, this approach has been used to treat four patients with Fanconi anemia. In a subsequent presentation, Dr. Jeffrey P. Kahn will review the ethics of creating such a stem cell donor. Originally used to help parents avoid bearing children affected by genetic disease, this extension of the use of pre-implantation genetic diagnosis raises many ethical, legal, and policy issues and promises to engender lively debate from both the scientific community and the public. Dr. Kahn will review some of these issues and raise the possibility that more oversight is needed as the potential generation of stem cell donors becomes more widespread. Finally, in this session, Dr. Irving L. Weissman will review the use of embryonic stem cells for the study of human disease.

In the Stem Cell Mobilization Education Session, the basic biology of hematopoietic stem cell mobilization will be reviewed along with presentations centered on the optimization of the collection of stem cells from both autologous and allogeneic donors. Initially, Dr. Tsvee Lapidot will discuss the many factors influencing stem cell mobilization and how the normal physiologic stem cell efflux from the bone marrow is altered by administration of cytokines. Emphasis will be placed on reviewing the roles of cytokines, adhesion molecules, stromalstem cell interactions, and chemokines. Subsequently, Dr. Michele H. Cottler-Fox will discuss strategies to optimize collection of mobilized hematopoietic stem cells and progenitors. Data will be reviewed regarding the current standard agents used in the clinic for mobilization and how best to monitor the donor to optimize the time of stem cell harvest. Newer agents for mobilization, including AMD3100, which targets the stem cellstromal cell interaction will also be covered. Finally, Dr. John DiPersio will review the clinical results of stem cell mobilization and transplantation in the setting of allogeneic donors. He will discuss the use of G-CSF, GMCSF, and the combination in terms of the number and type of cells that are collected. Studies evaluating the correlation between disease relapse and the source of stem cells (peripheral blood mobilized versus bone marrow) will be reviewed. Available data will also be presented regarding both the immunological reconstitution and graft versus host disease properties of mobilized, allogeneic cells.