NHLBI Home » Information for Patients and the Public » Express Home » Public Involvement |
Seventh Annual Public Interest Organization MeetingJanuary 30-31, 2006 – Bethesda, MarylandBreakout SessionsStem cell technology is a fast-growing and controversial field of research. The participants at the meeting had an opportunity to attend two sessions during which NHLBI staff described the advances and promise of this research. In two other sessions, the participants had an opportunity to learn about the NIH grants process, priority setting, and strategic planning, and about NHLBI cohort studies and gene research. Each session included a question-and-answer period. The State of Stem Cell Technology Today: Potential and Progress NIH 101: The Grants Process, Priority Setting, and Strategic Planning Stem Cells, Tissue Engineering, and Bioengineering for Therapy: "Oh Wow!" Science from a Clinician's Perspective NHLBI Cohort Studies and Genetic Research: What Can We Learn and How Much Do We Want to Know? The State of Stem Cell Technology Today: Potential and ProgressDrs. John Thomas and Traci Heath Mondoro, Health Science Administrators, Division of Blood Diseases and Resources, NHLBI, spoke about stem cell technology. Dr. Thomas focused on the potential of stem cells—the types, sources, and applications of stem cells and challenges in using stem cells. Dr. Mondoro summarized the progress made in manufacturing a stem cell product-one specific type of regulatory T cells—and the opportunities for using these cells therapeutically. The NHLBI actively supports stem cell research related to heart, lung, and blood diseases and resources. The Potential of Stem CellsDr. Thomas noted that interest in stem cells is at the forefront for two reasons:
Having these properties, stem cells are potentially useful in cell therapy for restoring tissues damaged by injury or disease. These cells have a tremendous ability to amplify—that is, produce a large number of cells. The three types of stems cells are:
Scientists have found stem cells in a range of tissues, including nerve, cornea, mouth, fat, skin, and gut tissues. The NHLBI supports research to identify possible stem cells in blood, lung, and heart tissues. Scientists derived and successfully cultured the first stem cells, which were embryonic stem cells from mice, 25 years ago. Publication of this achievement in 1981 was followed by a 1998 report on the successful derivation of human embryonic stem cells and establishment of stem cell lines from the isolated blastocysts. Dr. Thomas noted that stem cells may have three levels of potential. Some may be multipotent (e.g., blood stem cells), giving rise to all cells within a tissue or organ. Others may be pluripotent (e.g., embryonic stem cells), giving rise to all cells within the body. And, some may be totipotent (e.g., cells from a fertilized egg), giving rise to all cells within the body and the placenta and other supporting tissues. Scientists have particular interest in pluripotent cells because of their great promise. These cells may be derived from either blastocysts or fetal tissue. Dr. Thomas noted that the process of culturing pluripotent stem cells is difficult, time-consuming, and not always successful. Stem cells potentially could be used in cell therapy for treating cancers of the blood (e.g., leukemia, lymphoma), other cancers (by stimulating the immune system), genetic diseases (e.g., Fanconi's anemia, sickle cell disease), and tissue damage (e.g., injury to the heart or blood vessels). To treat heart damage, stem cells could be used to replace heart muscle cells, grow new blood vessels, and deliver cell growth factors. Stem cells also could be used to replace damaged or atherosclerotic blood vessels. Dr. Thomas emphasized that many challenges must be met before stem cells can be widely applied in cell therapy for patients. Considerable basic and preclinical research is still needed. The main research challenges are as follows: For use of autologous stem cells (i.e., those derived from the patient)—scientists need to determine the best source of these cells within the body, find ways to better identify and obtain the cells, and establish whether the cells can be expanded and differentiated into the cell type needed. In addition, it is not clear whether stem cells or only differentiated cells should be used, how the cells should be delivered, and which factors encourage long-term engrafting and functional integration of the cells into tissue. For use of allogeneic stem cells (i.e., donor cells)—two questions are paramount: Are the donor cells free of pathogens, genetic disease, and malignant cells? Will the immune system tolerate or reject the donor cells? Progress Made: Regulatory T CellsDr. Mondoro noted that scientists have been able to manufacture only a relatively small amount of stem cells. To scale up production and to ensure the safety of stem-cell products, cell processing centers are needed with both specialized skills and quality control. Dr. Mondoro described one study supported by the NHLBI to produce large quantities of pure CD4+/CD25+ regulatory T cells, which are derived from hematopoietic stem cells. She explained that T cells are a subset of white blood cells whose final stages of development occur in the thymus. There are three types of T cells: cytotoxic (which destroy infected cells), helper (which proliferate and produce cytokines to "help" other immune cells), and regulatory (which suppress activation of the immune system). Dr. Mondoro focused on regulatory T cells. She noted that the exact mechanism of their suppressive effects is not known and, yet, their failure to perform can result in autoimmune disease. CD4+ and CD25+ T cells are a small subset of T cells that regulate the function of other immune cells. Dr. Mondoro described the manufacturing process used to extract and culture quantities of pure CD4+ and CD25+ cells from donor blood. In the NHLBI study, the CD4+ and CD25+ cells are being developed for use in bone marrow transplantation, during which large numbers of these regulatory cells are needed at critical times to balance the dynamics between graft-versus-host and graft-versus-tumor effects. For example, as proposed for a clinical study at the University of Minnesota Cancer Center, regulatory T cells would be infused as adjunctive therapy during stem cell transplantation for patients with a hematologic malignancy and an available matched sibling donor. Dr. Mondoro noted that the CD4+ and CD25+ regulatory T cells also may be useful for replenishing T cell populations needed in patients with diabetes and for suppressing autoreactive myelin-specific T cells in patients with multiple sclerosis. Dr. Mondoro concluded by noting that the NHLBI currently provides support to three stem cell production centers. Participating in the NHLBI-sponsored Production Assistance for Cellular Therapies (PACT) Group, the centers are located at Baylor College of Medicine, University of Pittsburgh Medical Center, and University of Minnesota. The EMMES Corporation, in Rockville, Maryland, is the coordinating administrative center. The goal of PACT is to provide clinical-grade stem cells to researchers. NIH 101: The Grants Process, Priority Setting, and Strategic PlanningDr. Roth briefly discussed the organizational structure of the NIH, highlighting the NHLBI and the Center for Scientific Review (CSR), which is responsible for reviewing and scoring applications that are submitted to the NIH for research funding. He noted that although the NIH components have separate budgets and individual approaches to allocating funds among various activities, all ICs have similar organizational structures and procedures for funding grants and setting research priorities. NHLBI BudgetDr. Roth noted that the NHLBI budget comprises three broad areas, as follows:Extramural research—which constituted 91.3 percent of the FY 2005 budget. The funds are awarded as grants and contracts to researchers at universities, medical centers, and private companies. They support investigator-initiated research (amounting to approximately 68.2 percent of the extramural funds), institute-initiated research (approximately 28.5 percent), and training (approximately 3.3 percent). Investigator-initiated grant applications are submitted by researchers who select the research topic. Institute initiatives, in contrast, solicit applications and proposals that address topics selected by the NHLBI. Intramural research—which constituted 5.7 percent of the FY 2005 budget. The funds are used to support intramural researchers in laboratories on the NIH campus. Research management and support—which constituted 3.1 percent of the FY 2005 budget. The funds cover employee salaries and overhead, education and outreach programs, and activities such as the annual PIO meeting. The Grants ProcessDr. Roth summarized the NIH process for peer review of research grant applications. This process differs for investigator-initiated applications and institute-initiated research. He also commented on the review process for research training awards. Investigator-Initiated ApplicationsThe NIH uses a standardized process for evaluating and selecting investigator-initiated grant applications for funding. The CSR receives all applications and, based on the topic area of the application and on established referral guidelines, assigns each application to a CSR study section and the appropriate IC. The CSR study sections, which are composed of scientific experts in a particular field, meet three times a year to review grant applications. The study sections give each application a score that, when expressed as a percentile, reflects the application's scientific merit relative to other applications they review. The advisory council of the assigned IC conducts a secondary review of the grant applications assigned to the IC. At the NHLBI, the NHLBAC consists of 12 health research experts and 6 public interest members who meet four times a year. The NHLBI makes the final decision on whether to fund a particular grant based on the CSR percentile score, the NHLBAC recommendation, and budgetary considerations. Institute-Initiated ResearchIdeas for institute-initiated research come from a variety of sources, including NHBLI program staff and scientific experts who participate in Institute-sponsored workshops and task forces. NHLBI staff present proposed initiatives to the NHLBI Board of Extramural Advisors (BEA) for detailed discussion. The BEA, a group of experts representing scientific areas in the Institute's purview, ranks the initiatives. The director of the appropriate NHLBI extramural division and the NHLBI director review the rankings. The NHLBAC provides a final review. The NHLBI selects initiatives to announce to the scientific community based on the BEA and NHLBAC recommendations and on budgetary considerations. NHLBI staff members then prepare RFAs, PAs, and RFPs to invite researchers to apply for funding. Like investigator-initiated grant applications, grant applications received in response to RFAs and PAs are reviewed and awarded based on scientific merit. CSR study sections review applications received in response to PAs, and special emphasis panels convened by the NHLBI review applications received in response to RFAs and RFPs. Research TrainingThe NIH funds research training through National Research Service Awards (NRSAs) to institutions, who then select their own trainees, as well as through NRSAs to individuals (fellowships). All applications for training awards undergo a competitive review process to determine which applications will be funded. NHLBI Management of Grants and ContractsThe five NHLBI extramural divisions manage almost all of the grants and contracts funded by the NHLBI. The extramural divisions are as follows:
DiscussionIn response to questions, Dr. Roth addressed the following topics.Budget Constraints and Research FundingDr. Roth noted that current budget constraints may reduce the number of awards the NHLBI is able to fund. Criteria for Funding DecisionsDecisions about the allocation of NHLBI funds to various research areas develop differently for investigator- and institute-initiated research. Dr. Roth emphasized that decisions about the funding of investigator-initiated research occur virtually independent of the research area and topic of the grant application. The decisions are based on scientific merit, as judged during the review process. Institute-initiated research grants and contracts also are awarded based on scientific merit, but the NHLBI chooses the topic areas to fund based on scientific needs and opportunities and on whether the particular area is sufficiently represented by grants in NHLBI's investigator-initiated research portfolio. Coordination of NIH Research on Diseases Affecting Multiple Organ SystemsDr. Roth commented that ICs with an interest in the same research area or disease often issue joint initiatives. Stem Cells, Tissue Engineering, and Bioengineering for Therapy: |
Return to | Summary |
Return to | NIH: Overview and Roadmap Progress |
Return to | NHLBI: Vision for the Future |
Return to | NHLBI: Highlights of Success and Accomplishments |
Return to | Eliminating Post-Transfusion Hepatitis C Virus |
Return to | Blood Safety: A Personal Perspective |
|