Coriell Extends Its Scope

When New Jersey gave the Coriell Institute for Medical Research $5 million last year, it was the first time any state had funded an umbilical cord blood bank. But no other state has a research institute like Coriell, in Camden, across the Delaware River from Philadelphia. The nonprofit has, for nearly five decades, collected, stored, and cultured cells, providing them to almost every major research center worldwide. Courtesy of Coriell InstituteAn umbilical cord blood cassette used in storing the blood ensures that the contents remain free of contamination. The new bank will store the umbilical cord blood gathered from the state's newborns. "Having a readily available source of stem cells that can be transplanted into unrelated recipients will be a major advance," said David P. Beck, the institute's president, at the time of the bank's establishment last November. Cord blood research holds vast potential for therapeutic interventions. One day, it could even be possible to coax stem cells into taking on characteristics of other tissues by selected treatments and culture condition. The new bank will help Coriell with its ongoing research into cord blood, as well as provide a life-saving source of stem cells for bone marrow transplants. Since its founding in 1953, Coriell has provided millions of cell samples to researchers, serving as the basis for groundbreaking discoveries on Huntington's disease, Alzheimer's disease, hypercholesterolemia, retinitis pigmentosa, and manic-depressive illness, among others, according to Coriell. The institute is highly regarded by many in the research arena. "They're such a valuable resource to investigators in the United States and throughout the world," says Haig H. Kazazian Jr., genetics department chairman at the University of Pennsylvania, who has used Coriell cell lines for his own genetics studies. "Coriell has outstanding facilities and expertise with development of cell lines, managing complex conditions and information bases associated with the various human collections that they curate, and providing leadership in quality control," says Jeanne Altmann, ecology and evolutionary biology professor at Princeton University and co-investigator for the Primate Bioinformatics and Information Resource, a joint project in the planning stages. With just 20 faculty members, Coriell sits in an area rich in science and medical research: it is adjacent to the University of Medicine and Dentistry of New Jersey (UMDNJ) and Cooper Hospital, and across the river from institutions including Penn, Temple University, and Thomas Jefferson University. Coriell faculty members, who are affiliated with the UMDNJ and other schools, now represent several new disciplines, including cellular and molecular biology, human genetics, and physical anthropology. When Lewis L. Coriell founded this institute for basic research, it was the country's first major cell repository. Primarily funded by private gifts, contracts, and grants from the National Institutes of Health, American Diabetes Association, and the Juvenile Diabetes Foundation, Coriell holds cell lines from more than half of the 4,000 or so known genetic diseases. Since housing the first National Institutes of Health repository in 1964, Coriell has distributed more than 120,000 cell lines and nearly 100,000 DNA samples to researchers in 55 nations, resulting in more than 12,000 articles. The institute's DNA and cell repository continues to expand, as does its budget, which, thanks to increased grants and contracts, has tripled since 1990, increasing from about $3 million to more than $9 million in 2000. Such growth has led to expanded on-site research, and in recent years the institute launched programs in breast and prostate cancer, stem cell, and human genetic variations. In the first known effort of its kind, Coriell is spearheading an effort to collect and catalog cell and DNA samples from the entire range of nonhuman primates. This monumental project, which involves hundreds of samples from zoos, museums, and the wild, is expected to form the basis for comparative genomics of human and nonhuman primates. The project, if it proceeds as planned, will be based jointly at Coriell and the San Diego Zoo. The institute's collections and research efforts are closely related. "Going back to the beginning, we have been focused on our core technology: the handling and storage of human cells," says Beck. "We are primarily interested in understanding human disease and human genomics." Now, in many cases, work at Coriell serves the dual purpose of adding to the cell collections and furthering scientific understanding. Stem Cell Research One day the new cord blood bank will hold thousands of units of this rich resource, serving the state's 8 million residents. Cord blood offers a valuable alternative to bone marrow transplantation for treating leukemia, and ongoing research suggests that it holds treatment potential for many other serious diseases, such as cancer. "The New Jersey Cord Blood Bank is an important public service and, important to my own interests, a fantastic resource for research in this area," says Richard D. Huhn, the cord blood bank's director and associate professor at Coriell. His Coriell-based research has been published in journals like Blood,1 Immunopharmacology,2 and Human Gene Therapy.3 Huhn's current work involves amplifying the number of hematopoietic stem cells found in cord blood. This would provide readily available grafts for allogeneic transplantation to treat adult cancer and leukemia patients who do not have matched donors. (The stem cells harvested from a typical unit of cord blood are only enough for transplantation in a small child.) Courtesy of Coriell InstituteThe Coriell Institute keeps its cord blood and other cell samples in cryogenic storage. "We are working on optimizing the conditions for culture of hematopoietic cells from cord blood to expand the number of durably engrafting progenitor cells," Huhn says. His team is also studying how amplification affects the successfulness of stem cell transplantation, and looking at ways to improve gene transfer, by transplantation, into hematopoietic progenitor cells to correct genetic deficiencies. And, the institute hopes to investigate trans-differentiation, which is coaxing stem cells into taking on characteristics of other tissues, Huhn says. These treated cells then could be used to correct cell defects that underlie many inborn or acquired diseases. Future targets could include neurological diseases such as Parkinson's, central nervous system injuries, muscular dystrophies, cartilage damaged by arthritis, liver cells damaged by hepatic toxins, heart cells damaged by myocardial infarctions or virus infections, according to Huhn. Other Coriell researchers are examining cellular differentiation mechanisms and isolation of special cell types from cord blood and other tissues. The institute recently hired Rick I. Cohen, a differentiation-mechanisms specialist whose focus is on neuronal stem cells. Cohen is looking at the genetic factors that control cord blood stem cells' differentiation into neural lineages by using a combination of flow cytometry and microarray analysis. "The scientific understanding of the use of these cells should expand exponentially, given the recent advances in the public and private arms of the human genome project and the genetic screening technologies such as microarrays," says Cohen. "We will be able to use these genetic tools to understand what these cells are, and what we can make them into." Genetic Variations Research In other disease-related work, Coriell has brought in two visiting professors to conduct genetic variations studies on DNA samples taken from people in Sardinia, Italy. The population is mostly homogenous with origins from the late Neolithic era, about 2900 b.c. The 1.8 million inhabitants are divided into 363 villages, isolated for centuries because of mountains, rivers, and other natural barriers. Marriage and birth records date back to the 1600s. "Sardinia provides an ideal scenario to estimate the genetic and the environmental factors in determining complex phenotypes," said Renato Robledo, visiting professor, laboratory of human genetic variation at Coriell. "The Coriell Institute is an ideal place to conduct genetic studies." After conducting studies on villagers in Carloforte,4 Robledo and colleagues recently identified a chromosome locus for high myopia. "We found an unusually high frequency of high myopia in Carloforte, a rare disease in Sardinia," he says. "Most likely, the high myopia was brought in by the founder group."5 Using a sampling of 15 unrelated patients and 35 controls of this well-defined Mendelian breeding unit, the researchers found the locus on chromosome 18. Robledo indicated that he hopes that the research will help identify genes involved in multi-factorial traits and diseases, like diabetes, hypertension and cancer. His team also is working to describe polymorphisms in different populations. Cell lines collected in Sardinia will eventually be available to the worldwide scientific community. Genetic Diversity In another effort that could have lasting influence on science, the institute is heading the new Primate Biomaterials and Information Resource. The goal is to collect and catalog cell and DNA samples from the entire range of nonhuman primates. A collaboration between researchers at various institutions nationwide, Coriell is charged with processing, characterizing, and distributing the biomaterials collected, which will come from numerous sources, including blood, cell lines, scat, hair, and museum specimens. The National Science Foundation is expected to fund the project. "Elucidating the forces shaping intra-specific variation, the genetics of speciation, and the interaction of natural selection and genomic factors are critical objectives for evolutionary genetics," said Jeanne C. Beck, deputy director, Coriell cell repositories. Beck, who is married to David Beck, listed several studies that might develop, such as one that compares primate genomes to determine their evolutionary relationships, and comparing human and higher primate genomes to see the real extent of genetic variation and the origin of phenotypic differences. The new resource could help identify the regulatory elements and genetic changes underlying the traits unique to humans, Jeanne Beck says. The genetic difference between humans and primates is only three-tenths of a percent. That small percentage covers the genes that regulate development. The samples might help researchers find answers as to why nonhuman primates don't develop certain diseases, such as Alzheimer's, and how this information can help humans. Coriell also is working to find techniques to obtain noninvasive samples, says Altmann, which are of increasing importance in social and behavioral sciences and in conservation. A key processing component will be an extensive quality assurance and quality control system designed to ensure the sterility, viability, identity, and security of the biomaterials housed at Coriell. "These activities are precisely what Coriell has been providing to government agencies, private foundations, and investigators for almost 40 years," says Jeanne Beck. "Since many of the methods used in cell culture were developed at Coriell, it seems natural that this should be our role." Jennifer Fisher Wilson (jfwilson@snip.net) is a contributing editor for The Scientist. References 1. R.D. Huhn et al., "Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers," Blood, 87:699-705, 1996. 2. R.D. Huhn et al., "Effects of single intravenous doses of recombinant human interleukin-10 on subsets of circulating leukocytes in humans," Immunopharmacology, 41[2]:109-17, 1999. 3. R.D. Huhn et al., "Retroviral marking and transplantation of rhesus hematopoietic cells by nonmyeloablative conditioning," Human Gene Therapy, 10:1783-90, 1999. 4. M. Siniscalco et al., "Population genomics in Sardinia: a novel approach to hunt for genomic combinations underlying complex traits and diseases," Cytogentics and Cell Genetics, 86[2]:148-52, 1999. 5. See also, R. Lewis, "Founder populations fuel gene discovery," The Scientist, 15[8]:8, April 16, 2001.

Coriell Extends Its Scope

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